Abstract
Mitochondria serve as a vital energy source for nerve cells. The mitochondrial network also acts as a defense mechanism against external stressors that can threaten the stability of the nervous system. However, excessive accumulation of damaged mitochondria can lead to neuronal death. Mitophagy is an essential pathway in the mitochondrial quality control system and can protect neurons by selectively removing damaged mitochondria. In most neurological disorders, dysfunctional mitochondria are a common feature, and drugs that target mitophagy can improve symptoms. Here, we reviewed the role of mitophagy in Alzheimer’s disease, Parkinson’s disease, amyotrophic lateral sclerosis, Huntington’s disease, stroke, and traumatic brain injuries. We also summarized drug and non-drug approaches to promote mitophagy and described their therapeutic role in neurological disorders in order to provide valuable insight into the potential therapeutic agents available for neurological disease treatment. However, most studies on mitophagy regulation are based on preclinical research using cell and animal models, which may not accurately reflect the effects in humans. This poses a challenge to the clinical application of drugs targeting mitophagy. Additionally, these drugs may carry the risk of intolerable side effects and toxicity. Future research should focus on the development of safer and more targeted drugs for mitophagy.
Graphical abstract
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
Data availability
Not applicable.
References
Abulwerdi F, Liao C, Liu M, Azmi AS, Aboukameel A, Mady ASA, Gulappa T, Cierpicki T, Owens S, Zhang T, Sun D, Stuckey JA, Mohammad RM, Nikolovska-Coleska Z (2014) A novel small-molecule inhibitor of Mcl-1 blocks pancreatic cancer growth in vitro and in vivo. Mol Cancer Ther 13:565–575. https://doi.org/10.1158/1535-7163.MCT-12-0767
Ahluwalia M, Kumar M, Ahluwalia P, Rahimi S, Vender JR, Raju RP, Hess DC, Baban B, Vale FL, Dhandapani KM, Vaibhav K (2021) Rescuing mitochondria in traumatic brain injury and intracerebral hemorrhages—a potential therapeutic approach. Neurochem Int 150:105192. https://doi.org/10.1016/j.neuint.2021.105192
Ahmedy OA, Abdelghany TM, El-Shamarka MEA, Khattab MA, El-Tanbouly DM (2022) Apigenin attenuates LPS-induced neurotoxicity and cognitive impairment in mice via promoting mitochondrial fusion/mitophagy: role of SIRT3/PINK1/Parkin pathway. Psychopharmacology 239:3903–3917. https://doi.org/10.1007/s00213-022-06262-x
Ambivero CT, Cilenti L, Main S, Zervos AS (2014) Mulan E3 ubiquitin ligase interacts with multiple E2 conjugating enzymes and participates in mitophagy by recruiting GABARAP. Cell Signal 26:2921–2929. https://doi.org/10.1016/j.cellsig.2014.09.004
Andreux PA, Blanco-Bose W, Ryu D, Burdet F, Ibberson M, Aebischer P, Auwerx J, Singh A, Rinsch C (2019) The mitophagy activator urolithin A is safe and induces a molecular signature of improved mitochondrial and cellular health in humans. Nat Metab 1:595–603. https://doi.org/10.1038/s42255-019-0073-4
Arya JK, Kumar R, Tripathi SS, Rizvi SI (2022) 3-Bromopyruvate, a caloric restriction mimetic, exerts a mitohormetic effect to provide neuroprotection through activation of autophagy in rats during aging. Biogerontology 23:641–652. https://doi.org/10.1007/s10522-022-09988-5
Ashrafi G, Schwarz TL (2013) The pathways of mitophagy for quality control and clearance of mitochondria. Cell Death Differ 20:31–42. https://doi.org/10.1038/cdd.2012.81
Atamna H, Atamna W, Al-Eyd G, Shanower G, Dhahbi JM (2015) Combined activation of the energy and cellular-defense pathways may explain the potent anti-senescence activity of methylene blue. Redox Biol 6:426–435. https://doi.org/10.1016/j.redox.2015.09.004
Báez-Becerra C, Filipello F, Sandoval-Hernández A, Arboleda H, Arboleda G (2018) Liver X Receptor agonist GW3965 regulates synaptic function upon amyloid beta exposure in hippocampal neurons. Neurotox Res 33:569–579. https://doi.org/10.1007/s12640-017-9845-3
Bang Y, Kwon Y, Kim M, Moon SH, Jung K, Choi HJ (2023) Ursolic acid enhances autophagic clearance and ameliorates motor and non-motor symptoms in Parkinson’s disease mice model. Acta Pharmacol Sin 44:752–765. https://doi.org/10.1038/s41401-022-00988-2
Barodia SK, Creed RB, Goldberg MS (2017) Parkin and PINK1 functions in oxidative stress and neurodegeneration. Brain Res Bull 133:51–59. https://doi.org/10.1016/j.brainresbull.2016.12.004
Bellot G, Garcia-Medina R, Gounon P, Chiche J, Roux D, Pouysségur J, Mazure NM (2009) Hypoxia-induced autophagy is mediated through hypoxia-inducible factor induction of BNIP3 and BNIP3L via their BH3 domains. Mol Cell Biol 29:2570–2581. https://doi.org/10.1128/MCB.00166-09
Bonvento G, Bolaños JP (2021) Astrocyte-neuron metabolic cooperation shapes brain activity. Cell Metab 33:1546–1564. https://doi.org/10.1016/j.cmet.2021.07.006
Bordoni M, Pansarasa O, Scarian E, Cristofani R, Leone R, Fantini V, Garofalo M, Diamanti L, Bernuzzi S, Gagliardi S, Carelli S, Poletti A, Cereda C (2022) Lysosomes dysfunction causes mitophagy impairment in PBMCs of sporadic ALS patients. Cells 11:1272. https://doi.org/10.3390/cells11081272
Burchell VS, Nelson DE, Sanchez-Martinez A, Delgado-Camprubi M, Ivatt RM, Pogson JH, Randle SJ, Wray S, Lewis PA, Houlden H, Abramov AY, Hardy J, Wood NW, Whitworth AJ, Laman H, Plun-Favreau H (2013) The Parkinson’s disease genes Fbxo7 and Parkin interact to mediate mitophagy. Nat Neurosci 16. https://doi.org/10.1038/nn.3489
Cai Y, Yang E, Yao X, Zhang X, Wang Q, Wang Y, Liu J, Fan W, Yi K, Kang C, Wu J (2020) FUNDC1-dependent mitophagy induced by tPA protects neurons against cerebral ischemia-reperfusion injury. Redox Biol 38:101792. https://doi.org/10.1016/j.redox.2020.101792
Campbell, B.C.V., Khatri, P., 2020. Stroke Lancet 396, 129–142. https://doi.org/10.1016/S0140-6736(20)31179-X
Castrejón-Jiménez NS, Leyva-Paredes K, Baltierra-Uribe SL, Castillo-Cruz J, Campillo-Navarro M, Hernández-Pérez AD, Luna-Angulo AB, Chacón-Salinas R, Coral-Vázquez RM, Estrada-García I, Sánchez-Torres LE, Torres-Torres C, García-Pérez BE (2019) Ursolic and Oleanolic acids induce mitophagy in A549 human lung cancer cells. Molecules 24:3444. https://doi.org/10.3390/molecules24193444
Cen X, Chen Y, Xu X, Wu R, He F, Zhao Q, Sun Q, Yi C, Wu J, Najafov A, Xia H (2020) Pharmacological targeting of MCL-1 promotes mitophagy and improves disease pathologies in an Alzheimer’s disease mouse model. Nat Commun 11:5731. https://doi.org/10.1038/s41467-020-19547-6
Cen X, Xu X, Xia H (2021) Targeting MCL1 to induce mitophagy is a potential therapeutic strategy for Alzheimer disease. Autophagy 17:818–819. https://doi.org/10.1080/15548627.2020.1860542
Chan DC (2020) Mitochondrial Dynamics and Its Involvement in Disease. Annu Rev Pathol 15:235–259. https://doi.org/10.1146/annurev-pathmechdis-012419-032711
Chao H, Lin C, Zuo Q, Liu Y, Xiao M, Xu X, Li Z, Bao Z, Chen H, You Y, Kochanek PM, Yin H, Liu N, Kagan VE, Bayır H, Ji J (2019) Cardiolipin-dependent mitophagy guides outcome after traumatic brain injury. J Neurosci 39:1930–1943. https://doi.org/10.1523/JNEUROSCI.3415-17.2018
Chen A, Kristiansen CK, Hong Y, Kianian A, Fang EF, Sullivan GJ, Wang J, Li X, Bindoff LA, Liang KX (2021a) Nicotinamide Riboside and Metformin ameliorate mitophagy defect in induced pluripotent stem cell-derived astrocytes with POLG mutations. Front Cell Dev Biol 9:737304. https://doi.org/10.3389/fcell.2021.737304
Chen D, Liu J-R, Cheng Y, Cheng H, He P, Sun Y (2020) Metabolism of Rhaponticin and activities of its metabolite, Rhapontigenin: a review. Curr Med Chem 27:3168–3186. https://doi.org/10.2174/0929867326666190121143252
Chen, J., He, H.-J., Ye, Q., Feng, F., Wang, W.-W., Gu, Y., Han, R., Xie, C., 2021b. Defective autophagy and mitophagy in Alzheimer’s disease: mechanisms and translational implications. Mol Neurobiol 58, 5289–5302. https://doi.org/10.1007/s12035-021-02487-7
Chen P, Liu X, Gu C, Zhong P, Song N, Li M, Dai Z, Fang X, Liu Z, Zhang J, Tang R, Fan S, Lin X (2022) A plant-derived natural photosynthetic system for improving cell anabolism. Nature 612:546–554. https://doi.org/10.1038/s41586-022-05499-y
Cho I, Song H, Cho JH (2020) Flavonoids mitigate neurodegeneration in aged Caenorhabditis elegans by mitochondrial uncoupling. Food Sci Nutr 8:6633–6642. https://doi.org/10.1002/fsn3.1956
Choi ML, Chappard A, Singh BP, Maclachlan C, Rodrigues M, Fedotova EI, Berezhnov AV, De S, Peddie CJ, Athauda D, Virdi GS, Zhang W, Evans JR, Wernick AI, Zanjani ZS, Angelova PR, Esteras N, Vinokurov AY, Morris K et al (2022) Pathological structural conversion of α-synuclein at the mitochondria induces neuronal toxicity. Nat Neurosci 25:1134–1148. https://doi.org/10.1038/s41593-022-01140-3
Choi, S.G., Shin, J., Lee, K.Y., Park, H., Kim, S.I., Yi, Y.Y., Kim, D.W., Song, H.-J., Shin, H.J., 2023. PINK1 siRNA-loaded poly(lactic-co-glycolic acid) nanoparticles provide neuroprotection in a mouse model of photothrombosis-induced ischemic stroke. Glia. https://doi.org/10.1002/glia.24339
Chong MC, Silva A, James PF, Wu SSX, Howitt J (2022) Exercise increases the release of NAMPT in extracellular vesicles and alters NAD + activity in recipient cells. Aging Cell 21:e13647. https://doi.org/10.1111/acel.13647
Christ MG, Huesmann H, Nagel H, Kern A, Behl C (2019) Sigma-1 receptor activation induces autophagy and increases proteostasis capacity in vitro and in vivo. Cells 8:211. https://doi.org/10.3390/cells8030211
Chu CT, Ji J, Dagda RK, Jiang JF, Tyurina YY, Kapralov AA, Tyurin VA, Yanamala N, Shrivastava IH, Mohammadyani D, Wang KZQ, Zhu J, Klein-Seetharaman J, Balasubramanian K, Amoscato AA, Borisenko G, Huang Z, Gusdon AM, Cheikhi A et al (2013) Cardiolipin externalization to the outer mitochondrial membrane acts as an elimination signal for mitophagy in neuronal cells. Nat Cell Biol 15:1197–1205. https://doi.org/10.1038/ncb2837
Cilia R, Laguna J, Cassani E, Cereda E, Pozzi NG, Isaias IU, Contin M, Barichella M, Pezzoli G (2017) Mucuna pruriens in Parkinson disease: a double-blind, randomized, controlled, crossover study. Neurology 89:432–438. https://doi.org/10.1212/WNL.0000000000004175
Clague MJ, Urbé S (2017) Integration of cellular ubiquitin and membrane traffic systems: focus on deubiquitylases. FEBS J 284:1753–1766. https://doi.org/10.1111/febs.14007
Cossu D, Yokoyama K, Sechi LA, Hattori N (2021) Potential of PINK1 and PARKIN proteins as biomarkers for active multiple sclerosis: a Japanese Cohort Study. Front Immunol 12:681386. https://doi.org/10.3389/fimmu.2021.681386
Crouzier L, Danese A, Yasui Y, Richard EM, Liévens J-C, Patergnani S, Couly S, Diez C, Denus M, Cubedo N, Rossel M, Thiry M, Su T-P, Pinton P, Maurice T, Delprat B (2022) Activation of the sigma-1 receptor chaperone alleviates symptoms of Wolfram syndrome in preclinical models. Sci Transl Med 14:eabh3763. https://doi.org/10.1126/scitranslmed.abh3763
D’Amico D, Andreux PA, Valdés P, Singh A, Rinsch C, Auwerx J (2021) Impact of the natural compound Urolithin A on health, disease, and aging. Trends Mol Med 27:687–699. https://doi.org/10.1016/j.molmed.2021.04.009
Davinelli S, De Stefani D, De Vivo I, Scapagnini G (2020) Polyphenols as caloric restriction mimetics regulating mitochondrial biogenesis and mitophagy. Trends Endocrinol Metab 31:536–550. https://doi.org/10.1016/j.tem.2020.02.011
Davis CO, Kim K-Y, Bushong EA, Mills EA, Boassa D, Shih T, Kinebuchi M, Phan S, Zhou Y, Bihlmeyer NA, Nguyen JV, Jin Y, Ellisman MH, Marsh-Armstrong N (2014) Transcellular degradation of axonal mitochondria. Proc Natl Acad Sci U S A 111:9633–9638. https://doi.org/10.1073/pnas.1404651111
Davis CO, Marsh-Armstrong N (2015) Discovery and implications of transcellular mitophagy. Autophagy 10:2383–2384. https://doi.org/10.4161/15548627.2014.981920
Di Rita A, Strappazzon F (n.d.) A protective variant of the autophagy receptor CALCOCO2/NDP52 in Multiple Sclerosis (MS). Autophagy 17:1565–1567. https://doi.org/10.1080/15548627.2021.1924969
Di Y, He Y-L, Zhao T, Huang X, Wu K-W, Liu S-H, Zhao Y-Q, Fan M, Wu L-Y, Zhu L-L (2015) Methylene blue reduces acute cerebral ischemic injury via the induction of mitophagy. Mol Med 21:420–429. https://doi.org/10.2119/molmed.2015.00038
Ding, H., Li, Y., Chen, S., Wen, Y., Zhang, S., Luo, E., Li, X., Zhong, W., Zeng, H., 2022a. Fisetin ameliorates cognitive impairment by activating mitophagy and suppressing neuroinflammation in rats with sepsis-associated encephalopathy. CNS Neurosci Ther 28, 247–258. https://doi.org/10.1111/cns.13765
Ding, X., Zhao, H., Qiao, C., 2022b. Icariin protects podocytes from NLRP3 activation by Sesn2-induced mitophagy through the Keap1-Nrf2/HO-1 axis in diabetic nephropathy. Phytomedicine 99, 154005. https://doi.org/10.1016/j.phymed.2022.154005
Drake JC, Wilson RJ, Laker RC, Guan Y, Spaulding HR, Nichenko AS, Shen W, Shang H, Dorn MV, Huang K, Zhang M, Bandara AB, Brisendine MH, Kashatus JA, Sharma PR, Young A, Gautam J, Cao R, Wallrabe H et al (2021) Mitochondria-localized AMPK responds to local energetics and contributes to exercise and energetic stress-induced mitophagy. Proc Natl Acad Sci U S A 118:e2025932118. https://doi.org/10.1073/pnas.2025932118
Erlich AT, Brownlee DM, Beyfuss K, Hood DA (2018) Exercise induces TFEB expression and activity in skeletal muscle in a PGC-1α-dependent manner. Am J Phys Cell Phys 314:C62–C72. https://doi.org/10.1152/ajpcell.00162.2017
Fan L, Zhaohong X, Xiangxue W, Yingying X, Xiao Z, Xiaoyan Z, Jieke Y, Chao L (2022) Melatonin ameliorates the progression of Alzheimer’s disease by inducing TFEB nuclear translocation, promoting mitophagy, and regulating NLRP3 inflammasome activity. Biomed Res Int 2022:8099459. https://doi.org/10.1155/2022/8099459
Fang EF (2019) Mitophagy and NAD+ inhibit Alzheimer disease. Autophagy 15:1112–1114. https://doi.org/10.1080/15548627.2019.1596497
Fang EF, Hou Y, Lautrup S, Jensen MB, Yang B, SenGupta T, Caponio D, Khezri R, Demarest TG, Aman Y, Figueroa D, Morevati M, Lee H-J, Kato H, Kassahun H, Lee J-H, Filippelli D, Okur MN, Mangerich A et al (2019a) NAD+ augmentation restores mitophagy and limits accelerated aging in Werner syndrome. Nat Commun 10:5284. https://doi.org/10.1038/s41467-019-13172-8
Fang EF, Hou Y, Palikaras K, Adriaanse BA, Kerr JS, Yang B, Lautrup S, Hasan-Olive MM, Caponio D, Dan X, Rocktäschel P, Croteau DL, Akbari M, Greig NH, Fladby T, Nilsen H, Cader MZ, Mattson MP, Tavernarakis N, Bohr VA (2019b) Mitophagy inhibits amyloid-β and tau pathology and reverses cognitive deficits in models of Alzheimer’s disease. Nat Neurosci 22:401–412. https://doi.org/10.1038/s41593-018-0332-9
Fang EF, Kassahun H, Croteau DL, Scheibye-Knudsen M, Marosi K, Lu H, Shamanna RA, Kalyanasundaram S, Bollineni RC, Wilson MA, Iser WB, Wollman BN, Morevati M, Li J, Kerr JS, Lu Q, Waltz TB, Tian J, Sinclair DA et al (2016) NAD+ replenishment improves lifespan and healthspan in Ataxia telangiectasia models via mitophagy and DNA repair. Cell Metab 24:566–581. https://doi.org/10.1016/j.cmet.2016.09.004
Fedotova EI, Dolgacheva LP, Abramov AY, Berezhnov AV (2022) Lactate and pyruvate activate autophagy and mitophagy that protect cells in toxic model of Parkinson’s disease. Mol Neurobiol 59:177–190. https://doi.org/10.1007/s12035-021-02583-8
Forte M, Marchitti S, Cotugno M, Di Nonno F, Stanzione R, Bianchi F, Schirone L, Schiavon S, Vecchio D, Sarto G, Scioli M, Raffa S, Tocci G, Relucenti M, Torrisi MR, Valenti V, Versaci F, Vecchione C, Volpe M et al (2021) Trehalose, a natural disaccharide, reduces stroke occurrence in the stroke-prone spontaneously hypertensive rat. Pharmacol Res 173:105875. https://doi.org/10.1016/j.phrs.2021.105875
Franco-Iborra S, Plaza-Zabala A, Montpeyo M, Sebastian D, Vila M, Martinez-Vicente M (n.d.) Mutant HTT (huntingtin) impairs mitophagy in a cellular model of Huntington disease. Autophagy 17:672–689. https://doi.org/10.1080/15548627.2020.1728096
Gan ZY, Callegari S, Cobbold SA, Cotton TR, Mlodzianoski MJ, Schubert AF, Geoghegan ND, Rogers KL, Leis A, Dewson G, Glukhova A, Komander D (2022) Activation mechanism of PINK1. Nature 602:328–335. https://doi.org/10.1038/s41586-021-04340-2
Gao L-J, Li P, Ma T, Zhong Z-Q, Xu S-J (2021) Ligustilide alleviates neurotoxicity in SH-SY5Y cells induced by Aβ25-35 via regulating endoplasmic reticulum stress and autophagy. Phytother Res 35:1572–1584. https://doi.org/10.1002/ptr.6925
Gao Y, Li J, Li J, Hu C, Zhang L, Yan J, Li L, Zhang L (2020) Tetrahydroxy stilbene glycoside alleviated inflammatory damage by mitophagy via AMPK related PINK1/Parkin signaling pathway. Biochem Pharmacol 177:113997. https://doi.org/10.1016/j.bcp.2020.113997
Gendi F, Pei F, Wang Y, Li H, Fu J, Chang C (2022) Mitochondrial proteins unveil the mechanism by which physical exercise ameliorates memory, learning and motor activity in hypoxic ischemic encephalopathy rat model. Int J Mol Sci 23:4235. https://doi.org/10.3390/ijms23084235
Gladkova C, Maslen S, Skehel JM, Komander D (2018) Mechanism of Parkin activation by PINK1. Nature 559:410–414. https://doi.org/10.1038/s41586-018-0224-x
González-Jiménez A, López-Cotarelo P, Agudo-Jiménez T, Casanova I, de Silanes CL, Martín-Requero Á, Matesanz F, Urcelay E, Espino-Paisán L (2022) Impact of multiple sclerosis risk polymorphism rs7665090 on MANBA activity, lysosomal endocytosis, and lymphocyte activation. Int J Mol Sci 23:8116. https://doi.org/10.3390/ijms23158116
Gross A, Katz SG (2017) Non-apoptotic functions of BCL-2 family proteins. Cell Death Differ 24:1348–1358. https://doi.org/10.1038/cdd.2017.22
Grossmann D, Berenguer-Escuder C, Chemla A, Arena G, Krüger R (2020) The emerging role of RHOT1/Miro1 in the pathogenesis of Parkinson’s disease. Front Neurol 11:587. https://doi.org/10.3389/fneur.2020.00587
Gu C, Li L, Huang Y, Qian D, Liu W, Zhang C, Luo Y, Zhou Z, Kong F, Zhao X, Liu H, Gao P, Chen J, Yin G (2020) Salidroside ameliorates mitochondria-dependent neuronal apoptosis after spinal cord ischemia-reperfusion injury partially through inhibiting oxidative stress and promoting mitophagy. Oxidative Med Cell Longev 2020:3549704. https://doi.org/10.1155/2020/3549704
Guan R, Zou W, Dai X, Yu X, Liu H, Chen Q, Teng W (2018) Mitophagy, a potential therapeutic target for stroke. J Biomed Sci 25:87. https://doi.org/10.1186/s12929-018-0487-4
Gumeni S, Papanagnou E-D, Manola MS, Trougakos IP (2021) Nrf2 activation induces mitophagy and reverses Parkin/Pink1 knock down-mediated neuronal and muscle degeneration phenotypes. Cell Death Dis 12:671. https://doi.org/10.1038/s41419-021-03952-w
Gureev AP, Sadovnikova IS, Starkov NN, Starkov AA, Popov VN (2020) p62-Nrf2-p62 Mitophagy regulatory loop as a target for preventive therapy of neurodegenerative diseases. Brain Sci 10:847. https://doi.org/10.3390/brainsci10110847
Gureev AP, Shaforostova EA, Popov VN, Starkov AA (2019) Methylene blue does not bypass Complex III antimycin block in mouse brain mitochondria. FEBS Lett 593:499–503. https://doi.org/10.1002/1873-3468.13332
Han X, Xu T, Fang Q, Zhang H, Yue L, Hu G, Sun L (2021) Quercetin hinders microglial activation to alleviate neurotoxicity via the interplay between NLRP3 inflammasome and mitophagy. Redox Biol 44:102010. https://doi.org/10.1016/j.redox.2021.102010
Han Y, Wang N, Kang J, Fang Y (2020) β-Asarone improves learning and memory in Aβ1-42-induced Alzheimer’s disease rats by regulating PINK1-Parkin-mediated mitophagy. Metab Brain Dis 35:1109–1117. https://doi.org/10.1007/s11011-020-00587-2
Haque MN, Hannan MA, Dash R, Choi SM, Moon IS (2021) The potential LXRβ agonist stigmasterol protects against hypoxia/reoxygenation injury by modulating mitophagy in primary hippocampal neurons. Phytomedicine 81:153415. https://doi.org/10.1016/j.phymed.2020.153415
Hardiman O, Al-Chalabi A, Chio A, Corr EM, Logroscino G, Robberecht W, Shaw PJ, Simmons Z, van den Berg LH (2017) Amyotrophic lateral sclerosis. Nat Rev Dis Primers 3:17071. https://doi.org/10.1038/nrdp.2017.71
Hassanpour M, Cheraghi O, Laghusi D, Nouri M, Panahi Y (2020) The relationship between ANT1 and NFL with autophagy and mitophagy markers in patients with multiple sclerosis. J Clin Neurosci 78:307–312. https://doi.org/10.1016/j.jocn.2020.04.122
Hayakawa K, Chan SJ, Mandeville ET, Park JH, Bruzzese M, Montaner J, Arai K, Rosell A, Lo EH (2018) Protective effects of endothelial progenitor cell-derived extracellular mitochondria in brain endothelium. Stem Cells 36:1404–1410. https://doi.org/10.1002/stem.2856
Hayakawa K, Esposito E, Wang X, Terasaki Y, Liu Y, Xing C, Ji X, Lo EH (2016) Transfer of mitochondria from astrocytes to neurons after stroke. Nature 535:551–555. https://doi.org/10.1038/nature18928
Hirai K, Aliev G, Nunomura A, Fujioka H, Russell RL, Atwood CS, Johnson AB, Kress Y, Vinters HV, Tabaton M, Shimohama S, Cash AD, Siedlak SL, Harris PLR, Jones PK, Petersen RB, Perry G, Smith MA (2001) Mitochondrial abnormalities in Alzheimer’s disease. J Neurosci 21:3017–3023. https://doi.org/10.1523/JNEUROSCI.21-09-03017.2001
Homayoun H (2018) Parkinson Disease. Ann Intern Med 169:ITC33–ITC48. https://doi.org/10.7326/AITC201809040
Hosseini L, Majdi A, Sadigh-Eteghad S, Farajdokht F, Ziaee M, Rahigh Aghsan S, Farzipour M, Mahmoudi J (2022) Coenzyme Q10 ameliorates aging-induced memory deficits via modulation of apoptosis, oxidative stress, and mitophagy in aged rats. Exp Gerontol 168:111950. https://doi.org/10.1016/j.exger.2022.111950
Hou M, Bao W, Gao Y, Chen J, Song G (2022) Honokiol improves cognitive impairment in APP/PS1 mice through activating mitophagy and mitochondrial unfolded protein response. Chem Biol Interact 351:109741. https://doi.org/10.1016/j.cbi.2021.109741
Hsieh C-H, Li L, Vanhauwaert R, Nguyen KT, Davis MD, Bu G, Wszolek ZK, Wang X (2019) Miro1 marks Parkinson’s disease subset and Miro1 reducer rescues neuron loss in Parkinson’s models. Cell Metab 30:1131–1140.e7. https://doi.org/10.1016/j.cmet.2019.08.023
Hsieh C-H, Shaltouki A, Gonzalez AE, da Cruz AB, Burbulla LF, St Lawrence E, Schüle B, Krainc D, Palmer TD, Wang X (2016) Functional impairment in Miro degradation and mitophagy is a shared feature in familial and sporadic Parkinson’s disease. Cell Stem Cell 19:709–724. https://doi.org/10.1016/j.stem.2016.08.002
Hu B, Li J, Gong D, Dai Y, Wang P, Wan L, Xu S (2022) Long-term consumption of food-derived chlorogenic acid protects mice against acetaminophen-induced hepatotoxicity via promoting PINK1-dependent mitophagy and inhibiting apoptosis. Toxics 10:665. https://doi.org/10.3390/toxics10110665
Hwang S, Disatnik M-H, Mochly-Rosen D (2015) Impaired GAPDH-induced mitophagy contributes to the pathology of Huntington’s disease. EMBO Mol Med 7:1307–1326. https://doi.org/10.15252/emmm.201505256
Ide K, Secher NH (2000) Cerebral blood flow and metabolism during exercise. Prog Neurobiol 61:397–414. https://doi.org/10.1016/s0301-0082(99)00057-x
Iriondo MN, Etxaniz A, Varela YR, Ballesteros U, Hervás JH, Montes LR, Goñi FM, Alonso A (2022) LC3 subfamily in cardiolipin-mediated mitophagy: a comparison of the LC3A, LC3B and LC3C homologs. Autophagy 18:2985–3003. https://doi.org/10.1080/15548627.2022.2062111
Jang S, Kang HT, Hwang ES (2012) Nicotinamide-induced mitophagy: event mediated by high NAD+/NADH ratio and SIRT1 protein activation. J Biol Chem 287:19304–19314. https://doi.org/10.1074/jbc.M112.363747
Jiang X, Cai S, Jin Y, Wu F, He J, Wu X, Tan Y, Wang Y (2021) Irisin attenuates oxidative stress, mitochondrial dysfunction, and apoptosis in the H9C2 cellular model of septic cardiomyopathy through augmenting Fundc1-dependent mitophagy. Oxidative Med Cell Longev 2021:2989974. https://doi.org/10.1155/2021/2989974
Jiao C, Gao F, Ou L, Yu J, Li M, Wei P, Miao F (2017) Tetrahydroxy stilbene glycoside (TSG) antagonizes Aβ-induced hippocampal neuron injury by suppressing mitochondrial dysfunction via Nrf2-dependent HO-1 pathway. Biomed Pharmacother 96:222–228. https://doi.org/10.1016/j.biopha.2017.09.134
Jin SM, Lazarou M, Wang C, Kane LA, Narendra DP, Youle RJ (2010) Mitochondrial membrane potential regulates PINK1 import and proteolytic destabilization by PARL. J Cell Biol 191:933–942. https://doi.org/10.1083/jcb.201008084
Jin SM, Youle RJ (2013) The accumulation of misfolded proteins in the mitochondrial matrix is sensed by PINK1 to induce PARK2/Parkin-mediated mitophagy of polarized mitochondria. Autophagy 9:1750–1757. https://doi.org/10.4161/auto.26122
Joshi AU, Minhas PS, Liddelow SA, Haileselassie B, Andreasson KI, Dorn GW, Mochly-Rosen D (2019) Fragmented mitochondria released from microglia trigger A1 astrocytic response and propagate inflammatory neurodegeneration. Nat Neurosci 22:1635–1648. https://doi.org/10.1038/s41593-019-0486-0
Kagan VE, Jiang J, Huang Z, Tyurina YY, Desbourdes C, Cottet-Rousselle C, Dar HH, Verma M, Tyurin VA, Kapralov AA, Cheikhi A, Mao G, Stolz D, St Croix CM, Watkins S, Shen Z, Li Y, Greenberg ML, Tokarska-Schlattner M et al (2016) NDPK-D (NM23-H4)-mediated externalization of cardiolipin enables elimination of depolarized mitochondria by mitophagy. Cell Death Differ 23:1140–1151. https://doi.org/10.1038/cdd.2015.160
Kang Y, Yin S, Liu J, Jiang Y, Huang Z, Chen L, Shao L (2022) Nano-graphene oxide depresses neurotransmission by blocking retrograde transport of mitochondria. J Hazard Mater 424:127660. https://doi.org/10.1016/j.jhazmat.2021.127660
Kataoka K, Bilkei-Gorzo A, Nozaki C, Togo A, Nakamura K, Ohta K, Zimmer A, Asahi T (2020) Age-dependent alteration in mitochondrial dynamics and autophagy in hippocampal neuron of cannabinoid CB1 receptor-deficient mice. Brain Res Bull 160:40–49. https://doi.org/10.1016/j.brainresbull.2020.03.014
Ke P-Y, Chang C-W, Hsiao Y-C (2022) Baicalein activates parkin-dependent mitophagy through NDP52 and OPTN. Cells 11:1132. https://doi.org/10.3390/cells11071132
Khalil B, Liévens J-C (2017) Mitochondrial quality control in amyotrophic lateral sclerosis: towards a common pathway? Neural Regen Res 12:1052–1061. https://doi.org/10.4103/1673-5374.211179
Kitada T, Asakawa S, Hattori N, Matsumine H, Yamamura Y, Minoshima S, Yokochi M, Mizuno Y, Shimizu N (1998) Mutations in the parkin gene cause autosomal recessive juvenile parkinsonism. Nature 392:605–608. https://doi.org/10.1038/33416
Kitagishi, Y., Kobayashi, M., Kikuta, K., Matsuda, S., 2012. Roles of PI3K/AKT/GSK3/mTOR Pathway in cell signaling of mental illnesses. Depress Res Treat 2012. https://doi.org/10.1155/2012/752563
Kluge AF, Lagu BR, Maiti P, Jaleel M, Webb M, Malhotra J, Mallat A, Srinivas PA, Thompson JE (2018) Novel highly selective inhibitors of ubiquitin specific protease 30 (USP30) accelerate mitophagy. Bioorg Med Chem Lett 28:2655–2659. https://doi.org/10.1016/j.bmcl.2018.05.013
Knopman DS, Amieva H, Petersen RC, Chételat G, Holtzman DM, Hyman BT, Nixon RA, Jones DT (2021) Alzheimer disease Nat Rev Dis Primers 7:33. https://doi.org/10.1038/s41572-021-00269-y
Komilova NR, Angelova PR, Berezhnov AV, Stelmashchuk OA, Mirkhodjaev UZ, Houlden H, Gourine AV, Esteras N, Abramov AY (2022) Metabolically induced intracellular pH changes activate mitophagy, autophagy, and cell protection in familial forms of Parkinson’s disease. FEBS J 289:699–711. https://doi.org/10.1111/febs.16198
Kondapalli C, Kazlauskaite A, Zhang N, Woodroof HI, Campbell DG, Gourlay R, Burchell L, Walden H, Macartney TJ, Deak M, Knebel A, Alessi DR, Muqit MMK (2012) PINK1 is activated by mitochondrial membrane potential depolarization and stimulates Parkin E3 ligase activity by phosphorylating Serine 65. Open Biol 2:120080. https://doi.org/10.1098/rsob.120080
Krutskikh EP, Potanina DV, Samoylova NA, Gryaznova MV, Sadovnikova IS, Gureev AP, Popov VN (2022) Brain protection by Methylene blue and its derivative, Azur B, via activation of the Nrf2/ARE pathway in cisplatin-induced cognitive impairment. Pharmaceuticals (Basel) 15:815. https://doi.org/10.3390/ph15070815
Kubasiak LA, Hernandez OM, Bishopric NH, Webster KA (2002) Hypoxia and acidosis activate cardiac myocyte death through the Bcl-2 family protein BNIP3. Proc Natl Acad Sci U S A 99:12825–12830. https://doi.org/10.1073/pnas.202474099
Lazarou M, Sliter DA, Kane LA, Sarraf SA, Wang C, Burman JL, Sideris DP, Fogel AI, Youle RJ (2015) The ubiquitin kinase PINK1 recruits autophagy receptors to induce mitophagy. Nature 524:309–314. https://doi.org/10.1038/nature14893
Lee J-H, Yang D-S, Goulbourne CN, Im E, Stavrides P, Pensalfini A, Chan H, Bouchet-Marquis C, Bleiwas C, Berg MJ, Huo C, Peddy J, Pawlik M, Levy E, Rao M, Staufenbiel M, Nixon RA (2022) Faulty autolysosome acidification in Alzheimer’s disease mouse models induces autophagic build-up of Aβ in neurons, yielding senile plaques. Nat Neurosci 25:688–701. https://doi.org/10.1038/s41593-022-01084-8
Leonetti C, Macrez R, Pruvost M, Hommet Y, Bronsard J, Fournier A, Perrigault M, Machin I, Vivien D, Clemente D, De Castro F, Maubert E, Docagne F (2017) Tissue-type plasminogen activator exerts EGF-like chemokinetic effects on oligodendrocytes in white matter (re)myelination. Mol Neurodegener 12:20. https://doi.org/10.1186/s13024-017-0160-5
Li R, Chen J (2019) Salidroside protects dopaminergic neurons by enhancing PINK1/Parkin-mediated mitophagy. Oxidative Med Cell Longev 2019:9341018. https://doi.org/10.1155/2019/9341018
Li S, Sheng Z-H (2022) Energy matters: presynaptic metabolism and the maintenance of synaptic transmission. Nat Rev Neurosci 23:4–22. https://doi.org/10.1038/s41583-021-00535-8
Li S, Sun X, Xu L, Sun R, Ma Z, Deng X, Liu B, Fu Q, Qu R, Ma S (2017) Baicalin attenuates in vivo and in vitro hyperglycemia-exacerbated ischemia/reperfusion injury by regulating mitochondrial function in a manner dependent on AMPK. Eur J Pharmacol 815:118–126. https://doi.org/10.1016/j.ejphar.2017.07.041
Li W, Fu Y, Halliday GM, Sue CM (2021) PARK genes link mitochondrial dysfunction and alpha-synuclein pathology in sporadic Parkinson’s disease. Front Cell Dev Biol 9:612476. https://doi.org/10.3389/fcell.2021.612476
Li Z, Cheng J, Liu J (2020) Baicalin protects human OA chondrocytes against IL-1β-induced apoptosis and ECM degradation by activating autophagy via MiR-766-3p/AIFM1 axis. Drug Des Devel Ther 14:2645–2655. https://doi.org/10.2147/DDDT.S255823
Liang J-R, Martinez A, Lane JD, Mayor U, Clague MJ, Urbé S (2015) USP30 deubiquitylates mitochondrial Parkin substrates and restricts apoptotic cell death. EMBO Rep 16:618–627. https://doi.org/10.15252/embr.201439820
Liang W, Huang X, Chen W (2017) The effects of Baicalin and Baicalein on cerebral ischemia: a review. Aging Dis 8:850–867. https://doi.org/10.14336/AD.2017.0829
Lin C, Chao H, Li Z, Xu X, Liu Y, Hou L, Liu N, Ji J (2016) Melatonin attenuates traumatic brain injury-induced inflammation: a possible role for mitophagy. J Pineal Res 61:177–186. https://doi.org/10.1111/jpi.12337
Liu B, Tian Y, Li Y, Wu P, Zhang Y, Zheng J, Shi H (2022) ACEA attenuates oxidative stress by promoting mitophagy via CB1R/Nrf1/PINK1 pathway after subarachnoid hemorrhage in rats. Oxidative Med Cell Longev 2022:1024279. https://doi.org/10.1155/2022/1024279
Liu J, Wang X, Lu Y, Duan C, Gao G, Lu L, Yang H (2017) Pink1 interacts with α-synuclein and abrogates α-synuclein-induced neurotoxicity by activating autophagy. Cell Death Dis 8:e3056. https://doi.org/10.1038/cddis.2017.427
Liu K, Jing M-J, Liu C, Yan D-Y, Ma Z, Wang C, Deng Y, Liu W, Xu B (2019) Effect of trehalose on manganese-induced mitochondrial dysfunction and neuronal cell damage in mice. Basic Clin Pharmacol Toxicol 125:536–547. https://doi.org/10.1111/bcpt.13316
Liu L, Feng D, Chen G, Chen M, Zheng Q, Song P, Ma Q, Zhu C, Wang R, Qi W, Huang L, Xue P, Li B, Wang X, Jin H, Wang J, Yang F, Liu P, Zhu Y et al (2012) Mitochondrial outer-membrane protein FUNDC1 mediates hypoxia-induced mitophagy in mammalian cells. Nat Cell Biol 14:177–185. https://doi.org/10.1038/ncb2422
Liu L, Li Y, Wang J, Zhang D, Wu H, Li W, Wei H, Ta N, Fan Y, Liu Y, Wang X, Wang J, Pan X, Liao X, Zhu Y, Chen Q (2021) Mitophagy receptor FUNDC1 is regulated by PGC-1α/NRF1 to fine tune mitochondrial homeostasis. EMBO Rep 22:e50629. https://doi.org/10.15252/embr.202050629
Liu L, Sakakibara K, Chen Q, Okamoto K (2014) Receptor-mediated mitophagy in yeast and mammalian systems. Cell Res 24:787–795. https://doi.org/10.1038/cr.2014.75
Liu Y, Lear TB, Verma M, Wang KZ, Otero PA, McKelvey AC, Dunn SR, Steer E, Bateman NW, Wu C, Jiang Y, Weathington NM, Rojas M, Chu CT, Chen BB, Mallampalli RK (2020) Chemical inhibition of FBXO7 reduces inflammation and confers neuroprotection by stabilizing the mitochondrial kinase PINK1. JCI Insight 5(e131834):131834. https://doi.org/10.1172/jci.insight.131834
Liu Y, Yan J, Sun C, Li G, Li S, Zhang L, Di C, Gan L, Wang Y, Zhou R, Si J, Zhang H (2018) Ameliorating mitochondrial dysfunction restores carbon ion-induced cognitive deficits via co-activation of NRF2 and PINK1 signaling pathway. Redox Biol 17:143–157. https://doi.org/10.1016/j.redox.2018.04.012
López-Doménech G, Howden JH, Covill-Cooke C, Morfill C, Patel JV, Bürli R, Crowther D, Birsa N, Brandon NJ, Kittler JT (2021) Loss of neuronal Miro1 disrupts mitophagy and induces hyperactivation of the integrated stress response. EMBO J 40:e100715. https://doi.org/10.15252/embj.2018100715
Lou G, Palikaras K, Lautrup S, Scheibye-Knudsen M, Tavernarakis N, Fang EF (2020) Mitophagy and neuroprotection. Trends Mol Med 26:8–20. https://doi.org/10.1016/j.molmed.2019.07.002
Luongo TS, Eller JM, Lu M-J, Niere M, Raith F, Perry C, Bornstein MR, Oliphint P, Wang L, McReynolds MR, Migaud ME, Rabinowitz JD, Johnson FB, Johnsson K, Ziegler M, Cambronne XA, Baur JA (2020) SLC25A51 is a mammalian mitochondrial NAD+ transporter. Nature 588:174–179. https://doi.org/10.1038/s41586-020-2741-7
Ma J, Ni H, Rui Q, Liu H, Jiang F, Gao R, Gao Y, Li D, Chen G (2019) Potential roles of NIX/BNIP3L Pathway in rat traumatic brain injury. Cell Transplant 28:585–595. https://doi.org/10.1177/0963689719840353
Ma L, Jia J, Niu W, Jiang T, Zhai Q, Yang L, Bai F, Wang Q, Xiong L (2015) Mitochondrial CB1 receptor is involved in ACEA-induced protective effects on neurons and mitochondrial functions. Sci Rep 5:12440. https://doi.org/10.1038/srep12440
MacDonald ME, Ambrose CM, Duyao MP, Myers RH, Lin C, Srinidhi L, Barnes G, Taylor SA, James M, Groot N, MacFarlane H (1993) A novel gene containing a trinucleotide repeat that is expanded and unstable on Huntington’s disease chromosomes. The Huntington’s Disease Collaborative Research Group. Cell 72:971–983. https://doi.org/10.1016/0092-8674(93)90585-e
Maiti AK, Saha NC, More SS, Panigrahi AK, Paul G (2017) Neuroprotective efficacy of mitochondrial antioxidant MitoQ in suppressing Peroxynitrite-mediated mitochondrial dysfunction inflicted by lead toxicity in the rat brain. Neurotox Res 31:358–372. https://doi.org/10.1007/s12640-016-9692-7
Mantle D, Heaton RA, Hargreaves IP (2021) Coenzyme Q10, ageing and the nervous system: an overview. Antioxidants (Basel) 11:2. https://doi.org/10.3390/antiox11010002
Manyam BV, Dhanasekaran M, Hare TA (2004) Neuroprotective effects of the antiparkinson drug Mucuna pruriens. Phytother Res 18:706–712. https://doi.org/10.1002/ptr.1514
Mao Y, Du J, Chen X, Al Mamun A, Cao L, Yang Y, Mubwandarikwa J, Zaeem M, Zhang W, Chen Y, Dai Y, Xiao J, Ye K (2022a) Maltol promotes mitophagy and inhibits oxidative stress via the Nrf2/PINK1/Parkin pathway after spinal cord injury. Oxidative Med Cell Longev 2022:1337630. https://doi.org/10.1155/2022/1337630
Mao Z, Tian L, Liu J, Wu Q, Wang N, Wang G, Wang Y, Seto S (2022b) Ligustilide ameliorates hippocampal neuronal injury after cerebral ischemia reperfusion through activating PINK1/Parkin-dependent mitophagy. Phytomedicine 101:154111. https://doi.org/10.1016/j.phymed.2022.154111
Mao Z, Yao M, Li Y, Fu Z, Li S, Zhang L, Zhou Z, Tang Q, Han X, Xia Y (2018) miR-96-5p and miR-101-3p as potential intervention targets to rescue TiO2 NP-induced autophagy and migration impairment of human trophoblastic cells. Biomater Sci 6:3273–3283. https://doi.org/10.1039/c8bm00856f
Martín-Maestro, P., Gargini, R., García, E., Perry, G., Avila, J., García-Escudero, V., 2017b. Slower dynamics and aged mitochondria in sporadic Alzheimer’s disease. Oxidative Med Cell Longev 2017, 9302761. https://doi.org/10.1155/2017/9302761
Martín-Maestro P, Gargini R, Perry G, Avila J, García-Escudero V (2016) PARK2 enhancement is able to compensate mitophagy alterations found in sporadic Alzheimer’s disease. Hum Mol Genet 25:792–806. https://doi.org/10.1093/hmg/ddv616
Martín-Maestro P, Gargini R, Sproul AA, García E, Antón LC, Noggle S, Arancio O, Avila J, García-Escudero V (2017a) Mitophagy failure in fibroblasts and iPSC-derived neurons of Alzheimer’s disease-associated Presenilin 1 mutation. Front Mol Neurosci 10:291. https://doi.org/10.3389/fnmol.2017.00291
McWilliams TG, Prescott AR, Montava-Garriga L, Ball G, Singh F, Barini E, Muqit MMK, Brooks SP, Ganley IG (2018) Basal mitophagy occurs independently of PINK1 in mouse tissues of high metabolic demand. Cell Metab 27:439–449.e5. https://doi.org/10.1016/j.cmet.2017.12.008
Mehrabani S, Bagherniya M, Askari G, Read MI, Sahebkar A (2020) The effect of fasting or calorie restriction on mitophagy induction: a literature review. J Cachexia Sarcopenia Muscle 11:1447–1458. https://doi.org/10.1002/jcsm.12611
Melhuish Beaupre LM, Brown GM, Gonçalves VF, Kennedy JL (2021) Melatonin’s neuroprotective role in mitochondria and its potential as a biomarker in aging, cognition and psychiatric disorders. Transl Psychiatry 11:339. https://doi.org/10.1038/s41398-021-01464-x
Memme JM, Erlich AT, Phukan G, Hood DA (2021) Exercise and mitochondrial health. J Physiol 599:803–817. https://doi.org/10.1113/JP278853
Mi Y, Qi G, Vitali F, Shang Y, Raikes AC, Wang T, Jin Y, Brinton RD, Gu H, Yin F (2023) Loss of fatty acid degradation by astrocytic mitochondria triggers neuroinflammation and neurodegeneration. Nat Metab 5:445–465. https://doi.org/10.1038/s42255-023-00756-4
Mijaljica D, Prescott M, Devenish RJ (2010) Mitophagy and mitoptosis in disease processes. Methods Mol Biol 648:93–106. https://doi.org/10.1007/978-1-60761-756-3_6
Mizunoe Y, Kobayashi M, Sudo Y, Watanabe S, Yasukawa H, Natori D, Hoshino A, Negishi A, Okita N, Komatsu M, Higami Y (2018) Trehalose protects against oxidative stress by regulating the Keap1-Nrf2 and autophagy pathways. Redox Biol 15:115–124. https://doi.org/10.1016/j.redox.2017.09.007
Moradi-Afrapoli F, Oufir M, Walter FR, Deli MA, Smiesko M, Zabela V, Butterweck V, Hamburger M (2016) Validation of UHPLC-MS/MS methods for the determination of kaempferol and its metabolite 4-hydroxyphenyl acetic acid, and application to in vitro blood-brain barrier and intestinal drug permeability studies. J Pharm Biomed Anal 128:264–274. https://doi.org/10.1016/j.jpba.2016.05.039
Moskal N, Riccio V, Bashkurov M, Taddese R, Datti A, Lewis PN, Angus McQuibban G (2020) ROCK inhibitors upregulate the neuroprotective Parkin-mediated mitophagy pathway. Nat Commun 11:88. https://doi.org/10.1038/s41467-019-13781-3
Motawe ZY, Abdelmaboud SS, Cuevas J, Breslin JW (2020) PRE-084 as a tool to uncover potential therapeutic applications for selective sigma-1 receptor activation. Int J Biochem Cell Biol 126:105803. https://doi.org/10.1016/j.biocel.2020.105803
Murphy MP (2009) How mitochondria produce reactive oxygen species. Biochem J 417:1–13. https://doi.org/10.1042/BJ20081386
Nixon RA (2013) The role of autophagy in neurodegenerative disease. Nat Med 19:983–997. https://doi.org/10.1038/nm.3232
Nunnari J, Suomalainen A (2012) Mitochondria. In Sickness and in Health Cell 148:1145. https://doi.org/10.1016/j.cell.2012.02.035
Osellame LD, Rahim AA, Hargreaves IP, Gegg ME, Richard-Londt A, Brandner S, Waddington SN, Schapira AHV, Duchen MR (2013) Mitochondria and quality control defects in a mouse model of Gaucher disease-links to Parkinson’s disease. Cell Metab 17:941–953. https://doi.org/10.1016/j.cmet.2013.04.014
Otsu K, Murakawa T, Yamaguchi O (2015) BCL2L13 is a mammalian homolog of the yeast mitophagy receptor Atg32. Autophagy 11:1932–1933. https://doi.org/10.1080/15548627.2015.1084459
Park K, Lim H, Kim J, Hwang Y, Lee YS, Bae SH, Kim H, Kim H, Kang S-W, Kim JY, Lee M-S (2022) Lysosomal Ca2+-mediated TFEB activation modulates mitophagy and functional adaptation of pancreatic β-cells to metabolic stress. Nat Commun 13:1300. https://doi.org/10.1038/s41467-022-28874-9
Patergnani S, Bonora M, Ingusci S, Previati M, Marchi S, Zucchini S, Perrone M, Wieckowski MR, Castellazzi M, Pugliatti M, Giorgi C, Simonato M, Pinton P (2021) Antipsychotic drugs counteract autophagy and mitophagy in multiple sclerosis. Proc Natl Acad Sci U S A 118:e2020078118. https://doi.org/10.1073/pnas.2020078118
Pavlovic D, Pekic S, Stojanovic M, Popovic V (2019) Traumatic brain injury: neuropathological, neurocognitive and neurobehavioral sequelae. Pituitary 22:270–282. https://doi.org/10.1007/s11102-019-00957-9
Perecko T, Jancinova V, Drabikova K, Nosal R, Harmatha J (2008) Structure-efficiency relationship in derivatives of stilbene. Comparison of resveratrol, pinosylvin and pterostilbene. Neuro Endocrinol Lett 29:802–805
Peruzzotti-Jametti L, Bernstock JD, Willis CM, Manferrari G, Rogall R, Fernandez-Vizarra E, Williamson JC, Braga A, van den Bosch A, Leonardi T, Krzak G, Kittel Á, Benincá C, Vicario N, Tan S, Bastos C, Bicci I, Iraci N, Smith JA et al (2021) Neural stem cells traffic functional mitochondria via extracellular vesicles. PLoS Biol 19:e3001166. https://doi.org/10.1371/journal.pbio.3001166
Peshattiwar V, Muke S, Kaikini A, Bagle S, Dighe V, Sathaye S (2020) Mechanistic evaluation of Ursolic acid against rotenone induced Parkinson’s disease- emphasizing the role of mitochondrial biogenesis. Brain Res Bull 160:150–161. https://doi.org/10.1016/j.brainresbull.2020.03.003
Petersen OH, Verkhratsky A (2016) Calcium and ATP control multiple vital functions. Philos Trans R Soc Lond Ser B Biol Sci 371:20150418. https://doi.org/10.1098/rstb.2015.0418
Pineda-Ramírez N, Alquisiras-Burgos I, Ortiz-Plata A, Ruiz-Tachiquín M-E, Espinoza-Rojo M, Aguilera P (2020) Resveratrol activates neuronal autophagy through AMPK in the ischemic brain. Mol Neurobiol 57:1055–1069. https://doi.org/10.1007/s12035-019-01803-6
Poddighe S, De Rose F, Marotta R, Ruffilli R, Fanti M, Secci PP, Mostallino MC, Setzu MD, Zuncheddu MA, Collu I, Solla P, Marrosu F, Kasture S, Acquas E, Liscia A (2014) Mucuna pruriens (Velvet bean) rescues motor, olfactory, mitochondrial and synaptic impairment in PINK1B9 Drosophila melanogaster genetic model of Parkinson’s disease. PLoS One 9:e110802. https://doi.org/10.1371/journal.pone.0110802
Polo S, Díaz AF, Gallardo N, Leánez S, Balboni G, Pol O (2019) Treatment with the delta opioid agonist UFP-512 alleviates chronic inflammatory and neuropathic pain: mechanisms implicated. Front Pharmacol 10:283. https://doi.org/10.3389/fphar.2019.00283
Prakash J, Chouhan S, Yadav SK, Westfall S, Rai SN, Singh SP (2014) Withania somnifera Alleviates Parkinsonian Phenotypes by Inhibiting Apoptotic Pathways in Dopaminergic Neurons. Neurochem Res 39:2527–2536. https://doi.org/10.1007/s11064-014-1443-7
Qiu J, Chen Y, Zhuo J, Zhang L, Liu J, Wang B, Sun D, Yu S, Lou H (2022a) Urolithin A promotes mitophagy and suppresses NLRP3 inflammasome activation in lipopolysaccharide-induced BV2 microglial cells and MPTP-induced Parkinson’s disease model. Neuropharmacology 207:108963. https://doi.org/10.1016/j.neuropharm.2022.108963
Qiu W-Q, Ai W, Zhu F-D, Zhang Y, Guo M-S, Law BY-K, Wu J-M, Wong VK-W, Tang Y, Yu L, Chen Q, Yu C-L, Liu J, Qin D-L, Zhou X-G, Wu A-G (2022b) Polygala saponins inhibit NLRP3 inflammasome-mediated neuroinflammation via SHP-2-Mediated mitophagy. Free Radic Biol Med 179:76–94. https://doi.org/10.1016/j.freeradbiomed.2021.12.263
Rai SN, Singh P (2020) Advancement in the modelling and therapeutics of Parkinson’s disease. J Chem Neuroanat 104:101752. https://doi.org/10.1016/j.jchemneu.2020.101752
Rai SN, Yadav SK, Singh D, Singh SP (2016) Ursolic acid attenuates oxidative stress in nigrostriatal tissue and improves neurobehavioral activity in MPTP-induced Parkinsonian mouse model. J Chem Neuroanat 71:41–49. https://doi.org/10.1016/j.jchemneu.2015.12.002
Reddy AP, Yin X, Sawant N, Reddy PH (2021) Protective effects of antidepressant citalopram against abnormal APP processing and amyloid beta-induced mitochondrial dynamics, biogenesis, mitophagy and synaptic toxicities in Alzheimer’s disease. Hum Mol Genet 30:847–864. https://doi.org/10.1093/hmg/ddab054
Riley JS, Tait SW (2020) Mitochondrial DNA in inflammation and immunity. EMBO Rep 21:e49799. https://doi.org/10.15252/embr.201949799
Roca-Agujetas, V., Barbero-Camps, E., Dios, C. de, Podlesniy, P., Abadin, X., Morales, A., Marí, M., Trullàs, R., Colell, A., 2021. Cholesterol alters mitophagy by impairing optineurin recruitment and lysosomal clearance in Alzheimer’s disease. Mol Neurodegener 16. https://doi.org/10.1186/s13024-021-00435-6
Rocca CJ, Goodman SM, Dulin JN, Haquang JH, Gertsman I, Blondelle J, Smith JLM, Heyser CJ, Cherqui S (2017) Transplantation of wild-type mouse hematopoietic stem and progenitor cells ameliorates deficits in a mouse model of Friedreich’s ataxia. Sci Transl Med 9:eaaj2347. https://doi.org/10.1126/scitranslmed.aaj2347
Rogers RS, Tungtur S, Tanaka T, Nadeau LL, Badawi Y, Wang H, Ni H-M, Ding W-X, Nishimune H (2017) Impaired mitophagy plays a role in denervation of neuromuscular junctions in ALS mice. Front Neurosci 11:473. https://doi.org/10.3389/fnins.2017.00473
Rogov VV, Suzuki H, Marinković M, Lang V, Kato R, Kawasaki M, Buljubašić M, Šprung M, Rogova N, Wakatsuki S, Hamacher-Brady A, Dötsch V, Dikic I, Brady NR, Novak I (2017) Phosphorylation of the mitochondrial autophagy receptor Nix enhances its interaction with LC3 proteins. Sci Rep 7:1131. https://doi.org/10.1038/s41598-017-01258-6
Rusilowicz-Jones EV, Jardine J, Kallinos A, Pinto-Fernandez A, Guenther F, Giurrandino M, Barone FG, McCarron K, Burke CJ, Murad A, Martinez A, Marcassa E, Gersch M, Buckmelter AJ, Kayser-Bricker KJ, Lamoliatte F, Gajbhiye A, Davis S, Scott HC et al (2020) USP30 sets a trigger threshold for PINK1–PARKIN amplification of mitochondrial ubiquitylation. Life Sci Alliance 3:e202000768. https://doi.org/10.26508/lsa.202000768
Ryan BJ, Hoek S, Fon EA, Wade-Martins R (2015) Mitochondrial dysfunction and mitophagy in Parkinson’s: from familial to sporadic disease. Trends Biochem Sci 40:200–210. https://doi.org/10.1016/j.tibs.2015.02.003
Ryu D, Mouchiroud L, Andreux PA, Katsyuba E, Moullan N, Nicolet-Dit-Félix AA, Williams EG, Jha P, Lo Sasso G, Huzard D, Aebischer P, Sandi C, Rinsch C, Auwerx J (2016) Urolithin A induces mitophagy and prolongs lifespan in C. elegans and increases muscle function in rodents. Nat Med 22:879–888. https://doi.org/10.1038/nm.4132
Sandoval H, Thiagarajan P, Dasgupta SK, Schumacher A, Prchal JT, Chen M, Wang J (2008) Essential role for Nix in autophagic maturation of erythroid cells. Nature 454:232–235. https://doi.org/10.1038/nature07006
Sato M, Sato K (2012) Maternal inheritance of mitochondrial DNA: degradation of paternal mitochondria by allogeneic organelle autophagy, allophagy. Autophagy 8:424–425. https://doi.org/10.4161/auto.19243
Sentelle RD, Senkal CE, Jiang W, Ponnusamy S, Gencer S, Selvam SP, Ramshesh VK, Peterson YK, Lemasters JJ, Szulc ZM, Bielawski J, Ogretmen B (2012) Ceramide targets autophagosomes to mitochondria and induces lethal mitophagy. Nat Chem Biol 8:831–838. https://doi.org/10.1038/nchembio.1059
Settembre C, Di Malta C, Polito VA, Garcia Arencibia M, Vetrini F, Erdin S, Erdin SU, Huynh T, Medina D, Colella P, Sardiello M, Rubinsztein DC, Ballabio A (2011) TFEB links autophagy to lysosomal biogenesis. Science 332:1429–1433. https://doi.org/10.1126/science.1204592
Shaltouki A, Hsieh C-H, Kim MJ, Wang X (2018) Alpha-synuclein delays mitophagy and targeting Miro rescues neuron loss in Parkinson’s models. Acta Neuropathol 136:607–620. https://doi.org/10.1007/s00401-018-1873-4
Shao Z, Dou S, Zhu J, Wang H, Xu D, Wang C, Cheng B, Bai B (2021) Apelin-36 protects HT22 cells against oxygen-glucose deprivation/reperfusion-induced oxidative stress and mitochondrial dysfunction by promoting SIRT1-mediated PINK1/Parkin-dependent mitophagy. Neurotox Res 39:740–753. https://doi.org/10.1007/s12640-021-00338-w
Shi Y, Jia M, Xu L, Fang Z, Wu W, Zhang Q, Chung P, Lin Y, Wang S, Zhang Y (2019) miR-96 and autophagy are involved in the beneficial effect of grape seed proanthocyanidins against high-fat-diet-induced dyslipidemia in mice. Phytother Res 33:1222–1232. https://doi.org/10.1002/ptr.6318
Shih Y-H, Chein Y-C, Wang J-Y, Fu Y-S (2004) Ursolic acid protects hippocampal neurons against kainate-induced excitotoxicity in rats. Neurosci Lett 362:136–140. https://doi.org/10.1016/j.neulet.2004.03.011
Shu L, Hu C, Xu M, Yu J, He H, Lin J, Sha H, Lu B, Engelender S, Guan M, Song Z (2021) ATAD3B is a mitophagy receptor mediating clearance of oxidative stress-induced damaged mitochondrial DNA. EMBO J 40:e106283. https://doi.org/10.15252/embj.2020106283
Singh F, Prescott AR, Rosewell P, Ball G, Reith AD, Ganley IG (2021) Pharmacological rescue of impaired mitophagy in Parkinson’s disease-related LRRK2 G2019S knock-in mice. Elife 10:e67604. https://doi.org/10.7554/eLife.67604
Singh SS, Rai SN, Birla H, Zahra W, Kumar G, Gedda MR, Tiwari N, Patnaik R, Singh RK, Singh SP (2018) Effect of chlorogenic acid supplementation in MPTP-intoxicated mouse. Front Pharmacol 9:757. https://doi.org/10.3389/fphar.2018.00757
Singh SS, Rai SN, Birla H, Zahra W, Rathore AS, Dilnashin H, Singh R, Singh SP (2020) Neuroprotective effect of chlorogenic acid on mitochondrial dysfunction-mediated apoptotic death of DA neurons in a Parkinsonian mouse model. Oxidative Med Cell Longev 2020:6571484. https://doi.org/10.1155/2020/6571484
Sorrentino V, Romani M, Mouchiroud L, Beck JS, Zhang H, D’Amico D, Moullan N, Potenza F, Schmid AW, Rietsch S, Counts SE, Auwerx J (2017) Enhancing mitochondrial proteostasis reduces amyloid-β proteotoxicity. Nature 552:187–193. https://doi.org/10.1038/nature25143
Strub GM, Paillard M, Liang J, Gomez L, Allegood JC, Hait NC, Maceyka M, Price MM, Chen Q, Simpson DC, Kordula T, Milstien S, Lesnefsky EJ, Spiegel S (2011) Sphingosine-1-phosphate produced by sphingosine kinase 2 in mitochondria interacts with prohibitin 2 to regulate complex IV assembly and respiration. FASEB J 25:600–612. https://doi.org/10.1096/fj.10-167502
Sun E, Zhang J, Deng Y, Wang J, Wu Q, Chen W, Ma X, Chen S, Xiang X, Chen Y, Wu T, Yang Y, Chen B (2022) Docosahexaenoic acid alleviates brain damage by promoting mitophagy in mice with ischaemic stroke. Oxidative Med Cell Longev 2022:3119649. https://doi.org/10.1155/2022/3119649
Szargel R, Shani V, Abd Elghani F, Mekies LN, Liani E, Rott R, Engelender S (2016) The PINK1, synphilin-1 and SIAH-1 complex constitutes a novel mitophagy pathway. Hum Mol Genet 25:3476–3490. https://doi.org/10.1093/hmg/ddw189
Tang Y-C, Tian H-X, Yi T, Chen H-B (2016) The critical roles of mitophagy in cerebral ischemia. Protein Cell 7:699–713. https://doi.org/10.1007/s13238-016-0307-0
Tasegian A, Singh F, Ganley IG, Reith AD, Alessi DR (2021) Impact of Type II LRRK2 inhibitors on signaling and mitophagy. Biochem J 478:3555–3573. https://doi.org/10.1042/BCJ20210375
Tauffenberger A, Fiumelli H, Almustafa S, Magistretti PJ (2019) Lactate and pyruvate promote oxidative stress resistance through hormetic ROS signaling. Cell Death Dis 10:653. https://doi.org/10.1038/s41419-019-1877-6
Tjahjono E, Pei J, Revtovich AV, Liu T-JE, Swadi A, Hancu MC, Tolar JG, Kirienko NV (2021) Mitochondria-affecting small molecules ameliorate proteostasis defects associated with neurodegenerative diseases. Sci Rep 11:17733. https://doi.org/10.1038/s41598-021-97148-z
Tong M, Zablocki D, Sadoshima J (2020) The role of Drp1 in mitophagy and cell death in the heart. J Mol Cell Cardiol 142:138–145. https://doi.org/10.1016/j.yjmcc.2020.04.015
Trempe J-F, Sauvé V, Grenier K, Seirafi M, Tang MY, Ménade M, Al-Abdul-Wahid S, Krett J, Wong K, Kozlov G, Nagar B, Fon EA, Gehring K (2013) Structure of parkin reveals mechanisms for ubiquitin ligase activation. Science 340:1451–1455. https://doi.org/10.1126/science.1237908
Usmani A, Shavarebi F, Hiniker A (2021) The cell biology of LRRK2 in Parkinson’s disease. Mol Cell Biol 41:e00660–e00620. https://doi.org/10.1128/MCB.00660-20
Van Humbeeck C, Cornelissen T, Hofkens H, Mandemakers W, Gevaert K, De Strooper B, Vandenberghe W (2011) Parkin interacts with Ambra1 to induce mitophagy. J Neurosci 31:10249–10261. https://doi.org/10.1523/JNEUROSCI.1917-11.2011
Vanmierlo T, Weingärtner O, van der Pol S, Husche C, Kerksiek A, Friedrichs S, Sijbrands E, Steinbusch H, Grimm M, Hartmann T, Laufs U, Böhm M, de Vries HE, Mulder M, Lütjohann D (2012) Dietary intake of plant sterols stably increases plant sterol levels in the murine brain. J Lipid Res 53:726–735. https://doi.org/10.1194/jlr.M017244
Varghese N, Werner S, Grimm A, Eckert A (2020) Dietary mitophagy enhancer: a strategy for healthy brain aging? Antioxidants (Basel) 9:932. https://doi.org/10.3390/antiox9100932
Villa E, Proïcs E, Rubio-Patiño C, Obba S, Zunino B, Bossowski JP, Rozier RM, Chiche J, Mondragón L, Riley JS, Marchetti S, Verhoeyen E, Tait SWG, Ricci J-E (2017) Parkin-independent mitophagy controls chemotherapeutic response in cancer cells. Cell Rep 20:2846–2859. https://doi.org/10.1016/j.celrep.2017.08.087
Vos M, Dulovic-Mahlow M, Mandik F, Frese L, Kanana Y, Haissatou Diaw S, Depperschmidt J, Böhm C, Rohr J, Lohnau T, König IR, Klein C (2021) Ceramide accumulation induces mitophagy and impairs β-oxidation in PINK1 deficiency. Proc Natl Acad Sci U S A 118:e2025347118. https://doi.org/10.1073/pnas.2025347118
Walle T, Hsieh F, DeLegge MH, Oatis JE, Walle UK (2004) High absorption but very low bioavailability of oral resveratrol in humans. Drug Metab Dispos 32:1377–1382. https://doi.org/10.1124/dmd.104.000885
Wang D-X, Yang Y, Huang X-S, Tang J-Y, Zhang X, Huang H-X, Zhou B, Liu B, Xiao H-Q, Li X-H, Yang P, Zou S-C, Liu K, Wang X-Y, Li X-S (2021a) Pramipexole attenuates neuronal injury in Parkinson’s disease by targeting miR-96 to activate BNIP3-mediated mitophagy. Neurochem Int 146:104972. https://doi.org/10.1016/j.neuint.2021.104972
Wang H, Jiang T, Li W, Gao N, Zhang T (2018) Resveratrol attenuates oxidative damage through activating mitophagy in an in vitro model of Alzheimer’s disease. Toxicol Lett 282:100–108. https://doi.org/10.1016/j.toxlet.2017.10.021
Wang M, Wan C, He T, Han C, Zhu K, Waddington JL, Zhen X (2021b) Sigma-1 receptor regulates mitophagy in dopaminergic neurons and contributes to dopaminergic protection. Neuropharmacology 196:108360. https://doi.org/10.1016/j.neuropharm.2020.108360
Wang N, Wang H, Pan Q, Kang J, Liang Z, Zhang R (2021c) The combination of β-Asarone and Icariin inhibits amyloid-β and reverses cognitive deficits by promoting mitophagy in models of Alzheimer’s disease. Oxidative Med Cell Longev 2021:7158444. https://doi.org/10.1155/2021/7158444
Wang W-W, Han R, He H-J, Li J, Chen S-Y, Gu Y, Xie C (2021d) Administration of quercetin improves mitochondria quality control and protects the neurons in 6-OHDA-lesioned Parkinson’s disease models. Aging (Albany NY) 13:11738–11751. https://doi.org/10.18632/aging.202868
Wang Y, Nartiss Y, Steipe B, McQuibban GA, Kim PK (2012) ROS-induced mitochondrial depolarization initiates PARK2/PARKIN-dependent mitochondrial degradation by autophagy. Autophagy 8:1462–1476. https://doi.org/10.4161/auto.21211
Wang Z, Lu M, Zhang Y, Ji W, Lei L, Wang W, Fang L, Wang L, Yu F, Wang J, Li Z, Wang J-R, Wang T, Dou F, Wang Q, Wang X, Li S, Ma Q, Xu R (2019) Disrupted-in-schizophrenia-1 protects synaptic plasticity in a transgenic mouse model of Alzheimer’s disease as a mitophagy receptor. Aging Cell 18:e12860. https://doi.org/10.1111/acel.12860
Wei Y, Chiang W-C, Sumpter R, Mishra P, Levine B (2017) Prohibitin 2 is an inner mitochondrial membrane mitophagy receptor. Cell 168:224–238.e10. https://doi.org/10.1016/j.cell.2016.11.042
Wilkaniec A, Lenkiewicz AM, Babiec L, Murawska E, Jęśko HM, Cieślik M, Culmsee C, Adamczyk A (2021) Exogenous alpha-synuclein evoked parkin downregulation promotes mitochondrial dysfunction in neuronal cells. Implications for Parkinson’s Disease Pathology Front Aging Neurosci 13:591475. https://doi.org/10.3389/fnagi.2021.591475
Woodbury A, Yu SP, Wei L, García P (2013) Neuro-modulating effects of honokiol: a review. Front Neurol 4:130. https://doi.org/10.3389/fneur.2013.00130
Wu Q, Liu J, Mao Z, Tian L, Wang N, Wang G, Wang Y, Seto S (2022) Ligustilide attenuates ischemic stroke injury by promoting Drp1-mediated mitochondrial fission via activation of AMPK. Phytomedicine 95:153884. https://doi.org/10.1016/j.phymed.2021.153884
Wu X, Li X, Liu Y, Yuan N, Li C, Kang Z, Zhang X, Xia Y, Hao Y, Tan Y (2018) Hydrogen exerts neuroprotective effects on OGD/R damaged neurons in rat hippocampal by protecting mitochondrial function via regulating mitophagy mediated by PINK1/Parkin signaling pathway. Brain Res 1698:89–98. https://doi.org/10.1016/j.brainres.2018.06.028
Xiao Y-Y, Xiao J-X, Wang X-Y, Wang T, Qu X-H, Jiang L-P, Tou F-F, Chen Z-P, Han X-J (2022) Metformin-induced AMPK activation promotes cisplatin resistance through PINK1/Parkin dependent mitophagy in gastric cancer. Front Oncol 12:956190. https://doi.org/10.3389/fonc.2022.956190
Xie C, Zhuang X-X, Niu Z, Ai R, Lautrup S, Zheng S, Jiang Y, Han R, Gupta TS, Cao S, Lagartos-Donate MJ, Cai C-Z, Xie L-M, Caponio D, Wang W-W, Schmauck-Medina T, Zhang J, Wang H, Lou G et al (2022) Amelioration of Alzheimer’s disease pathology by mitophagy inducers identified via machine learning and a cross-species workflow. Nat Biomed Eng 6:76–93. https://doi.org/10.1038/s41551-021-00819-5
Xie Q, Zhang L, Xie L, Zheng Y, Liu K, Tang H, Liao Y, Li X (2020) Z-ligustilide: a review of its pharmacokinetics and pharmacology. Phytother Res 34:1966–1991. https://doi.org/10.1002/ptr.6662
Xie Y, Zhou B, Lin M-Y, Wang S, Foust KD, Sheng Z-H (2015) Endolysosomal deficits augment mitochondria pathology in spinal motor neurons of asymptomatic fALS mice. Neuron 87:355–370. https://doi.org/10.1016/j.neuron.2015.06.026
Xin T, Lu C (2020) Irisin activates Opa1-induced mitophagy to protect cardiomyocytes against apoptosis following myocardial infarction. Aging (Albany NY) 12:4474–4488. https://doi.org/10.18632/aging.102899
Xu H, Deng R, Li ETS, Shen J, Wang M (2020a) Pinosylvin provides neuroprotection against cerebral ischemia and reperfusion injury through enhancing PINK1/Parkin mediated mitophagy and Nrf2 pathway. J Funct Foods 71:104019. https://doi.org/10.1016/j.jff.2020.104019
Xu X, Zhang Y, Cheng H, Zhou R (n.d.) SPATA33 functions as a mitophagy receptor in mammalian germline. Autophagy 17:1284–1286. https://doi.org/10.1080/15548627.2021.1909836
Xu Y, Zhi F, Mao J, Peng Y, Shao N, Balboni G, Yang Y, Xia Y (2020b) δ-opioid receptor activation protects against Parkinson’s disease-related mitochondrial dysfunction by enhancing PINK1/Parkin-dependent mitophagy. Aging (Albany NY) 12:25035–25059. https://doi.org/10.18632/aging.103970
Xu Y, Zhi F, Peng Y, Shao N, Khiati D, Balboni G, Yang Y, Xia Y (2019) δ-opioid receptor activation attenuates hypoxia/MPP+-induced downregulation of PINK1: a novel mechanism of neuroprotection against Parkinsonian injury. Mol Neurobiol 56:252–266. https://doi.org/10.1007/s12035-018-1043-7
Xu Y-J, Mei Y, Qu Z-L, Zhang S-J, Zhao W, Fang J-S, Wu J, Yang C, Liu S-J, Fang Y-Q, Wang Q, Zhang Y-B (2018) Ligustilide ameliorates memory deficiency in APP/PS1 transgenic mice via restoring mitochondrial dysfunction. Biomed Res Int 2018:4606752. https://doi.org/10.1155/2018/4606752
Xue H, Thaivalappil A, Cao K (2021) The potentials of methylene blue as an anti-aging drug. Cells 10:3379. https://doi.org/10.3390/cells10123379
Yadav SK, Rai SN, Singh SP (2017) Mucuna pruriens reduces inducible nitric oxide synthase expression in Parkinsonian mice model. J Chem Neuroanat 80:1–10. https://doi.org/10.1016/j.jchemneu.2016.11.009
Yan C, Gong L, Chen L, Xu M, Abou-Hamdan H, Tang M, Désaubry L, Song Z (2019) PHB2 (prohibitin 2) promotes PINK1-PRKN/Parkin-dependent mitophagy by the PARL-PGAM5-PINK1 axis. Autophagy 16:419–434. https://doi.org/10.1080/15548627.2019.1628520
Yang C, Hashimoto M, Lin QXX, Tan DQ, Suda T (2019a) Sphingosine-1-phosphate signaling modulates terminal erythroid differentiation through the regulation of mitophagy. Exp Hematol 72:47–59.e1. https://doi.org/10.1016/j.exphem.2019.01.004
Yang H, Shen H, Li J, Guo L-W (2019b) SIGMAR1/Sigma-1 receptor ablation impairs autophagosome clearance. Autophagy 15:1539–1557. https://doi.org/10.1080/15548627.2019.1586248
Yao Y, Ren Z, Yang R, Mei Y, Dai Y, Cheng Q, Xu C, Xu X, Wang S, Kim KM, Noh JH, Zhu J, Zhao N, Liu YU, Mao G, Sima J (2022) Salidroside reduces neuropathology in Alzheimer’s disease models by targeting NRF2/SIRT3 pathway. Cell Biosci 12:180. https://doi.org/10.1186/s13578-022-00918-z
Ye J-S, Chen L, Lu Y-Y, Lei S-Q, Peng M, Xia Z-Y (2019) Honokiol-mediated mitophagy ameliorates postoperative cognitive impairment induced by surgery/sevoflurane via inhibiting the activation of NLRP3 inflammasome in the hippocampus. Oxidative Med Cell Longev 2019:8639618. https://doi.org/10.1155/2019/8639618
Ye M, Wu H, Li S (2021) Resveratrol alleviates oxygen/glucose deprivation/reoxygenation-induced neuronal damage through induction of mitophagy. Mol Med Rep 23:73. https://doi.org/10.3892/mmr.2020.11711
Yin K, Lee J, Liu Z, Kim H, Martin DR, Wu D, Liu M, Xue X (2021) Mitophagy protein PINK1 suppresses colon tumor growth by metabolic reprogramming via p53 activation and reducing acetyl-CoA production. Cell Death Differ 28:2421–2435. https://doi.org/10.1038/s41418-021-00760-9
Young MF, Valaris S, Wrann CD (2019) A role for FNDC5/Irisin in the beneficial effects of exercise on the brain and in neurodegenerative diseases. Prog Cardiovasc Dis 62:172–178. https://doi.org/10.1016/j.pcad.2019.02.007
Yu H-Y, Zhu Y, Zhang X-L, Wang L, Zhou Y-M, Zhang F-F, Zhang H-T, Zhao X-M (2022) Baicalin attenuates amyloid β oligomers induced memory deficits and mitochondria fragmentation through regulation of PDE-PKA-Drp1 signalling. Psychopharmacology 239:851–865. https://doi.org/10.1007/s00213-022-06076-x
Yu K, Li N, Cheng Q, Zheng J, Zhu M, Bao S, Chen M, Shi G (2018) miR-96-5p prevents hepatic stellate cell activation by inhibiting autophagy via ATG7. J Mol Med (Berl) 96:65–74. https://doi.org/10.1007/s00109-017-1593-6
Yun, J., Puri, R., Yang, H., Lizzio, M.A., Wu, C., Sheng, Z.-H., Guo, M., 2014. MUL1 acts in parallel to the PINK1/parkin pathway in regulating mitofusin and compensates for loss of PINK1/parkin eLife 3, e01958. https://doi.org/10.7554/eLife.01958
Zhang L, Dai L, Li D (2021) Mitophagy in neurological disorders. J Neuroinflammation 18:297. https://doi.org/10.1186/s12974-021-02334-5
Zhang T, Wu P, Budbazar E, Zhu Q, Sun C, Mo J, Peng J, Gospodarev V, Tang J, Shi H, Zhang JH (2019) Mitophagy reduces oxidative stress via Keap1/Nrf2/PHB2 pathway after SAH in rats. Stroke 50:978–988. https://doi.org/10.1161/STROKEAHA.118.021590
Zhang Y, Zhang T, Li Y, Guo Y, Liu B, Tian Y, Wu P, Shi H (2022) Metformin attenuates early brain injury after subarachnoid hemorrhage in rats via AMPK-dependent mitophagy. Exp Neurol 353:114055. https://doi.org/10.1016/j.expneurol.2022.114055
Zhao M, Wang Y, Li L, Liu S, Wang C, Yuan Y, Yang G, Chen Y, Cheng J, Lu Y, Liu J (2021) Mitochondrial ROS promote mitochondrial dysfunction and inflammation in ischemic acute kidney injury by disrupting TFAM-mediated mtDNA maintenance. Theranostics 11:1845–1863. https://doi.org/10.7150/thno.50905
Zhao N, Zhang X, Li B, Wang J, Zhang C, Xu B (2023) Treadmill exercise improves PINK1/Parkin-mediated mitophagy activity against Alzheimer’s disease pathologies by upregulated SIRT1-FOXO1/3 Axis in APP/PS1 mice. Mol Neurobiol 60:277–291. https://doi.org/10.1007/s12035-022-03035-7
Zhong G, Long H, Zhou T, Liu Y, Zhao J, Han J, Yang X, Yu Y, Chen F, Shi S (2022) Blood-brain barrier permeable nanoparticles for Alzheimer’s disease treatment by selective mitophagy of microglia. Biomaterials 288:121690. https://doi.org/10.1016/j.biomaterials.2022.121690
Zhong Z, Han J, Zhang J, Xiao Q, Hu J, Chen L (2018) Pharmacological activities, mechanisms of action, and safety of salidroside in the central nervous system. Drug Des Devel Ther 12:1479–1489. https://doi.org/10.2147/DDDT.S160776
Zhou H, Li D, Zhu P, Hu S, Hu N, Ma S, Zhang Y, Han T, Ren J, Cao F, Chen Y (2017a) Melatonin suppresses platelet activation and function against cardiac ischemia/reperfusion injury via PPARγ/FUNDC1/mitophagy pathways. J Pineal Res 63. https://doi.org/10.1111/jpi.12438
Zhou H, Zhang Y, Hu S, Shi C, Zhu P, Ma Q, Jin Q, Cao F, Tian F, Chen Y (2017b) Melatonin protects cardiac microvasculature against ischemia/reperfusion injury via suppression of mitochondrial fission-VDAC1-HK2-mPTP-mitophagy axis. J Pineal Res 63:e12413. https://doi.org/10.1111/jpi.12413
Zhu W-L, Zheng J-Y, Cai W-W, Dai Z, Li B-Y, Xu T-T, Liu H-F, Liu X-Q, Wei S-F, Luo Y, Wang H, Pan H-F, Wang Q, Zhang S-J (2020) Ligustilide improves aging-induced memory deficit by regulating mitochondrial related inflammation in SAMP8 mice. Aging (Albany NY) 12:3175–3189. https://doi.org/10.18632/aging.102793
Zhu Y, Massen S, Terenzio M, Lang V, Chen-Lindner S, Eils R, Novak I, Dikic I, Hamacher-Brady A, Brady NR (2013) Modulation of Serines 17 and 24 in the LC3-interacting Region of Bnip3 determines Pro-survival mitophagy versus apoptosis. J Biol Chem 288:1099–1113. https://doi.org/10.1074/jbc.M112.399345
Zorov DB, Juhaszova M, Sollott SJ (2014) Mitochondrial reactive oxygen species (ROS) and ROS-induced ROS release. Physiol Rev 94:909–950. https://doi.org/10.1152/physrev.00026.2013
Zucchi E, Ticozzi N, Mandrioli J (2019) Psychiatric symptoms in amyotrophic lateral sclerosis: beyond a motor neuron disorder. Front Neurosci 13:175. https://doi.org/10.3389/fnins.2019.00175
Funding
This work was financially supported by the National Natural Science Foundation of China (Grant No. 81901296) and Sichuan Science and Technology Program (Grant No. 2022NSFSC0758).
Author information
Authors and Affiliations
Contributions
Original concept: Xiong Yang and Mei-Hong Lu; writing—original draft of the review: Xiong Yang and Yu Zhang; prepared table and figures: Xiong Yang, Jia-xin Luo, Tao Zhu, and Zhao Ran; writing—review and editing Ben-Rong Mu and Mei-Hong Lu. The authors confirm that no paper mill and artificial intelligence was used.
Corresponding authors
Ethics declarations
Ethics approval
Not applicable.
Competing interests
The authors declare no competing interests.
Additional information
Publisher’s note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Rights and permissions
Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.
About this article
Cite this article
Yang, X., Zhang, Y., Luo, Jx. et al. Targeting mitophagy for neurological disorders treatment: advances in drugs and non-drug approaches. Naunyn-Schmiedeberg's Arch Pharmacol 396, 3503–3528 (2023). https://doi.org/10.1007/s00210-023-02636-w
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00210-023-02636-w