Abstract
Mitochondrial dynamics is a complex process, which involves the fission and fusion of mitochondrial outer and inner membranes. These processes organize the mitochondrial size and morphology, as well as their localization throughout the cells. In the last two decades, it has become a spotlight due to their importance in the pathophysiological processes, particularly in neurological diseases. It is known that Drp1, mitofusin 1 and 2, and Opa1 constitute the core of proteins that coordinate this intricate and dynamic process. Likewise, changes in the levels of reactive oxygen species (ROS) lead to modifications in the expression and/or activity of the proteins implicated in the mitochondrial dynamics, suggesting an involvement of these molecules in the process. In this review, we discuss the role of ROS in the regulation of fusion/fission in the nervous system, as well as the involvement of mitochondrial dynamics proteins in neurodegenerative diseases.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Alavi MV, Bette S, Schimpf S, Schuettauf F, Schraermeyer U, Wehrl HF, Wissinger B (2007) A splice site mutation in the murine Opa1 gene features pathology of autosomal dominant optic atrophy. Brain 130(4):1029–1042. https://doi.org/10.1093/brain/awm005
Alexander C, Votruba M, Pesch UE, Thiselton DL, Mayer S, Moore A, Wissinger B (2000) OPA1, encoding a dynamin-related GTPase, is mutated in autosomal dominant optic atrophy linked to chromosome 3q28. Nat Genet 26(2):211–215. https://doi.org/10.1038/79944
Altanbyek V, Cha SJ, Kang GU, Im DS, Lee S, Kim HJ, Kim K (2016) Imbalance of mitochondrial dynamics in Drosophila models of amyotrophic lateral sclerosis. Biochem Biophys Res Commun 481(3–4):259–264. https://doi.org/10.1016/j.bbrc.2016.10.134
Amati-Bonneau P, Milea D, Bonneau D, Chevrollier A, Ferré M, Guillet V, Reynier P (2009) OPA1-associated disorders: phenotypes and pathophysiology. Int J Biochem Cell Biol 41(10):1855–1865. https://doi.org/10.1016/j.biocel.2009.04.012
Amchenkova AA, Bakeeva LE, Chentsov YS, Skulachev VP, Zorov DB (1988) Coupling membranes as energy-transmitting cables. I. Filamentous mitochondria in fibroblast and mitochondrial clusters in cardiomyocytes. J Cell Sci 107(2):481–495. https://doi.org/10.1083/jcb.107.2.481
Anand R, Wai T, Baker MJ, Kladt N, Schauss AC, Rugarli E, Langer T (2014) The i-AAA protease YME1L and OMA1 cleave OPA1 to balance mitochondrial fusion and fission. J Cell Biol 204(6):919–929. https://doi.org/10.1083/jcb.201308006
Andreyev AY, Kushnareva YE, Murphy AN, Starkov AA, Diego S, Jolla L, Jolla L (2015) Mitochondrial ROS Metabolism: 10 Years Later A. HHS Pub Access 80(5):517–531. https://doi.org/10.1134/S0006297915050028
Angelova PR, Abramov AY (2016) Functional role of mitochondrial reactive oxygen species in physiology. Free Radic Biol Med 100:81–85. https://doi.org/10.1016/j.freeradbiomed.2016.06.005
Azzedine H, Senderek J, Rivolta C, Chrast R (2012) Molecular genetics of charcot-marie-tooth disease: from genes to genomes. Mol Syndromol. 3(5):204–214. https://doi.org/10.1159/000343487
Balog J, Mehta SL, Vemuganti R (2016) Mitochondrial fission and fusion in secondary brain damage after CNS insults. J Cereb Blood Flow Metab. https://doi.org/10.1177/0271678X16671528
Bertholet AM, Millet AM, Guillermin O, Daloyau M, Davezac N, Miquel MC, Belenguer P (2013) OPA1 loss of function affects in vitro neuronal maturation. Brain 136(5):1518–1533. https://doi.org/10.1093/brain/awt060
Bertholet AM, Delerue T, Millet AM, Moulis MF, David C, Daloyau M, Belenguer P (2016) Mitochondrial fusion/fission dynamics in neurodegeneration and neuronal plasticity. Neurobiol Dis 90:3–19. https://doi.org/10.1016/j.nbd.2015.10.011
Bleazard W, McCaffery JM, King EJ, Bale S, Mozdy A, Tieu Q, Nunnari J, Shaw JM (1999) The dynamin-related GTPase Dnm1 regulates mitochondrial fission in yeast. Nat Cell Biol 1(5):298–304. https://doi.org/10.1038/13014
Bleazard W, Mccaffery JM, King EJ, Bale S, Mozdy A, Tieu Q, Shaw JM (2013) The dynamin-related GTPase Dnm1 regulates mitochondrial fission in yeast. Nat Cell Biol 1(5):298–304. https://doi.org/10.1038/13014
Burte F, Carelli V, Chinnery PF, Yu-Wai-Man P (2015) Disturbed mitochondrial dynamics and neurodegenerative disorders. Nat Rev Neurol 11(1):11–24. https://doi.org/10.1038/nrneurol.2014.228
Cagalinec M, Safiulina D, Liiv M, Liiv J, Choubey V, Wareski P, Veksier V, Kaasik A (2013) Principles of the mitochondrial fusion and fission cycle in neurons. J Cell Sci 126:2187–2197. https://doi.org/10.1242/jcs.118844
Cereghetti GM, Stangherlin A, de Brito OM, Chang CR, Blackstone C, Bernardi P, Scorrano L (2008) Dephosphorylation by calcineurin regulates translocation of Drp1 to mitochondria. PNAS 105(41):15803–15808. https://doi.org/10.1073/pnas.0808249105
Chang CR, Blackstone C (2007a) Cyclic AMP-dependent protein kinase phosphorylation of Drp1 regulates its GTPase activity and mitochondrial morphology. J Biol Chem 282(30):21583–21587. https://doi.org/10.1074/jbc.C700083200
Chang CR, Blackstone C (2007b) Drp1 phosphorylation and mitochondrial regulation. EMBO Rep 8(12):1088–1089. https://doi.org/10.1038/sj.embor.7401118
Chang CR, Manlandro CM, Arnoult D, Stadler J, Posey AE, Hill RB, Blackstone C (2010) A lethal de novo mutation in the middle domain of the dynamin-related GTPase Drp1 impairs higher order assembly and mitochondrial division. J Biol Chem 285(42):32494–32503. https://doi.org/10.1074/jbc.M110.142430
Chao de la Barca JM, Prunier-Mirebeau D, Amati-Bonneau P, Ferré M, Sarzi E, Bris C, Reynier P (2016) OPA1-related disorders: diversity of clinical expression, modes of inheritance and pathophysiology. Neurobiol Dis 90:20–26. https://doi.org/10.1016/j.nbd.2015.08.015
Chen H, Detmer SA, Ewald AJ, Griffin EE, Fraser SE, Chan DC (2003) Mitofusins Mfn1 and Mfn2 coordinately regulate mitochondrial fusion and are essential for embryonic development. J Cell Biol 160(2):189–200. https://doi.org/10.1083/jcb.200211046
Chiang YY, Chen SL, Hsiao YT, Huang CH, Lin TY, Chiang IP, Chow KC (2009) Nuclear expression of dynamin-related protein 1 in lung adenocarcinomas. Mod Pathol 22(9):1139–1150. https://doi.org/10.1038/modpathol.2009.83
Cho D, Nakamura T, Fang J, Cieplak P, Gu Z, Lipton SA (2009) S-Nitrosylation of Drp1 mediates β-amyloid–related mitochondrial fission and neuronal injury. PNAS Injury 324(5923):1–11. https://doi.org/10.1126/science.1171091
Cho DH, Nakamura T, Lipton SA (2010) Mitochondrial dynamics in cell death and neurodegeneration. Cell Mol Life Sci 67(20):3435–3447. https://doi.org/10.1007/s00018-010-0435-2
Cho MH, Kim DH, Choi JE, Chang EJ, Seung-Yongyoon (2012) Increased phosphorylation of dynamin-related protein 1 and mitochondrial fission in okadaic acid-treated neurons. Brain Res 1454:100–110. https://doi.org/10.1016/j.brainres.2012.03.010
Correia SC, Santos RX, Perry G, Zhu X, Moreira PI, Smith MA (2012) Mitochondrial importance in Alzheimer’s, Huntington’s and Parkinson’s diseases. Adv Exp Med Biol 724:205–221. https://doi.org/10.1007/978-1-4614-0653-2_16
Cribbs JT, Strack S (2007) Reversible phosphorylation of Drp1 by cyclic AMP-dependent protein kinase and calcineurin regulates mitochondrial fission and cell death. EMBO Rep 8(10):939–944. https://doi.org/10.1038/sj.embor.7401062
Cuesta A, Pedrola L, Sevilla T, García-Planells J, Chumillas MJ, Mayordomo F, Palau F (2002) The gene encoding ganglioside-induced differentiation-associated protein 1 is mutated in axonal Charcot-Marie-Tooth type 4A disease. Nat Genet 30(1):22–25. https://doi.org/10.1038/ng798
Dankwa L, Richardson J, Motley WW, Züchner S, Scherer SS (2018) A mutation in the heptad repeat 2 domains of MFN2 in a large CMT2A family. J Peripher Nerv Syst. https://doi.org/10.1111/jns.12248
Delettre C, Lenaers G, Griffoin JM, Gigarel N, Lorenzo C, Belenguer P, Hamel CP (2000) Nuclear gene OPA1, encoding a mitochondrial dynamin-related protein, is mutated in dominant optic atrophy. Nat Genet 26(2):207–210. https://doi.org/10.1038/79936
Delettre C, Griffoin JM, Kaplan J, Dollfus H, Lorenz B, Faivre L, Hamel C (2001) Mutation spectrum and splicing variants in the OPA1 gene. Hum Genet 109(6):584–591. https://doi.org/10.1007/s00439-001-0633
Devoto MP, Dimopoulos N, Alloatti M, Pardi MB, Saez TM, Otero MG, Falzone TL (2017) αsynuclein control of mitochondrial homeostasis in human-derived neurons is disrupted by mutations associated with Parkinson’s disease. Sci Rep 7(1):1–13. https://doi.org/10.1038/s41598-017-05334-9
Dietrich MO, Liu ZW, Horvath TL (2013) Mitochondrial dynamics controlled by mitofusins regulate Agrp neuronal activity and diet-induced obesity. Cell 155(1):188–199. https://doi.org/10.1016/j.cell.2013.09.004
Ehses S, Raschke I, Mancuso G, Bernacchia A, Geimer S, Tondera D, Langer T (2009) Regulation of OPA1 processing and mitochondrial fusion by m-AAA protease isoenzymes and OMA1. J Cell Biol 187(7):1023–1036. https://doi.org/10.1083/jcb.200906084
Filichia E, Hoffer B, Qi X, Luo Y (2016) Inhibition of Drp1 mitochondrial translocation provides neural protection in dopaminergic system in a Parkinson’s disease model induced by MPTP. Sci Rep. https://doi.org/10.1038/srep32656
Fischer TD, Hylin MJ, Zhao J, Moore AN, Waxham MN, Dash PK (2016) Altered mitochondrial dynamics and TBI pathophysiology. Front Syst Neurosci. https://doi.org/10.3389/fnsys.2016.00029
Flippo KH, Strack S (2017) An emerging role for mitochondrial dynamics in schizophrenia. Schizophr Res 187:26–32. https://doi.org/10.1016/j.schres.2017.05.003
Frezza C (2017) Mitochondrial metabolites: undercover signalling molecules. Interface Focus 7(2):20160100. https://doi.org/10.1098/rsfs.2016.0100
Frezza C, Cipolat S, Martins de Brito O, Micaroni M, Beznoussenko GV, Rudka T, Bartoli D, Polishuck RS, Danial NN, De Strooper B, Scorrano L (2006) OPA1 controls apoptotic cristae remodeling independently from mitochondrial fusion. Cell 126(1):177–189. https://doi.org/10.1016/j.cell.2006.06.025
Galluzzi L, Bravo-San Pedro JM, Kroemer G (2014) Organelle-specific initiation of cell death. Nat Cell Biol 16(8):728–736. https://doi.org/10.1038/ncb3005
Gao J, Wang L, Liu J, Xie F, Su B, Wang X (2017) Abnormalities of mitochondrial dynamics in neurodegenerative diseases. Antioxidants 6(2):25. https://doi.org/10.3390/antiox6020025
Gautier CA, Erpapazoglou Z, Mouton-Liger F, Muriel MP, Cormier F, Bigou S, Duffaure S, Girard M, Foret B, Iannielli A, Broccoli V, Dalle C, Bohl D, Michel PP, Corvol JC, Brice A, Corti O (2016) The endoplasmic reticulum-mitochondria interface is perturbed in PARK2 knockout mice and patients with PARK2 mutations. Hum Mol Genet. https://doi.org/10.1093/hmg/ddw148
Gegg ME, Cooper JM, Chau KY, Rojo M, Schapira AH, Taanman JW (2010) Mitofusin 1 and mitofusin 2 are ubiquitinated in a PINK1/parkin-dependent manner upon induction of mitophagy. Hum Mol Gen 19(24):4861–4870. https://doi.org/10.1093/hmg/ddq419
Gomes LC, Di Benedetto G, Scorrano L (2011) During autophagy mitochondria elongate, are spared from degradation and sustain cell viability. Nat Cell Biol 13(5):589–598. https://doi.org/10.1038/ncb2220
Gray JJ, Zommer AE, Bouchard RJ, Duval N, Blackstone C, Linseman DA (2013) N-terminal cleavage of the mitochondrial fusion GTPase OPA1 occurs via a caspase-independent mechanism in cerebellar granule neurons exposed to oxidative or nitrosative stress. Brain Res 1494:28–43. https://doi.org/10.1016/j.brainres.2012.12.001
Guerra de Souza AC, Prediger RD, Cimarosti H (2016) SUMO-regulated mitochondrial function in Parkinson’s disease. J Neurochem 137(5):673–686. https://doi.org/10.1111/jnc.13599
Guo K, Lu J, Huang Y, Wu M, Zhang L, Yu H, Jia W (2015) Protective role of PGC-1α in diabetic nephropathy is associated with the inhibition of ROS through mitochondrial dynamic remodeling. PLoS ONE 10(4):1–16. https://doi.org/10.1371/journal.pone.0125176
Han XJ, Lu YF, Li SA, Kaitsuka T, Sato Y, Tomizawa K, Nairn AC, Takei K, Matsui H, Matsushita M (2008) CaM kinase I alpha-induced phosphorylation of Drp1 regulates mitochondrial morphology. J Cell Biol 182(3):573–585. https://doi.org/10.1083/jcb.200802164
Han XJ, Hu YY, Yang ZJ, Jiang LP, Shi SL, Li YR, Wan YY (2017) Amyloid β-42 induces neuronal apoptosis by targeting mitochondria. Mol Med Rep 16(4):4521–4528. https://doi.org/10.3892/mmr.2017.7203
Hering T, Kojer K, Birth N, Hallitsch J, Taanman JW, Orth M (2017) Mitochondrial cristae remodelling is associated with disrupted OPA1 oligomerisation in the Huntington’s disease R6/2 fragment model. Exp Neurol 288:167–175. https://doi.org/10.1016/j.expneurol.2016.10.017
Hom JR, Gewandter JS, Michael L, Sheu SS, Yoon Y (2007) Thapsigargin induces biphasic fragmentation of mitochondria through calcium-mediated mitochondrial fission and apoptosis. J Cell Physiol 212(2):498–508. https://doi.org/10.1002/jcp.21051
Huang P, Galloway CA, Yoon Y (2011) Control of mitochondrial morphology through differential interactions of mitochondrial fusion and fission proteins. PLoS ONE 6(5):e20655. https://doi.org/10.1371/journal.pone.0020655
Huang X, Sun L, Zhao T, Zhang W, Xu J, Cheng H (2013) Kissing and nanotunneling mediate intermitochondrial communication in the heart. PNAS 110(8):2846–2851. https://doi.org/10.1073/pnas.1300741110
Hung HC, Cheng SS, Cheung Y, Wuwongse S, Zhang NQ, Ho Y, Lee SM, Chang RC (2018) A reciprocal relationship between reactive oxygen species and mitochondrial dynamics in neurodegeneration. Redox Biol 14:7–19. https://doi.org/10.1016/j.redox.2017.08.010
Ingerman E, Perkins EM, Marino M, Mears JA, McCaffery JM, Hinshaw JE, Nunnari J (2005) Dnm1 forms spirals that are structurally tailored to fit mitochondria. J Cell Biol 170(7):1021–1027. https://doi.org/10.1083/jcb.200506078
Ishihara N, Fujita Y, Oka T, Mihara K (2006) Regulation of mitochondrial morphology through proteolytic cleavage of OPA1. EMBO 25(13):2966–2977. https://doi.org/10.1038/sj.emboj.7601184
Ishihara N, Nomura M, Jofuku A, Kato H, Suzuki SO, Masuda K, Mihara K (2009) Mitochondrial fission factor Drp1 is essential for embryonic development and synapse formation in mice. Nat Cell Biol 11(8):958–966. https://doi.org/10.1038/ncb1907
Itoh K, Nakamura K, Iijima M, Sesaki H (2013) Mitochondrial dynamics in neurodegeneration. Trends Cell Biol 23(2):64–71. https://doi.org/10.1016/j.tcb.2012.10.006
Jahani-Asl A, Cheung E, Neuspiel M, MacLaurin J, Fortin A, Park D, McBride H, Slack R (2007) Mitofusin 2 protects cerebellar granule neurons against injury-induced cell death. J Biol Chem 282(33):23788–23798. https://doi.org/10.1074/jbc.M703812200
Jahani-Asl A, Pilon-Larose K, Xu W, MacLaurin JG, Park DS, McBride HM, Slack RS (2011) The mitochondrial inner membrane GTPase, optic atrophy 1 (Opa1), restores mitochondrial morphology and promotes neuronal survival following excitotoxicity. J Biol Chem 286(6):4772–4782. https://doi.org/10.1074/jbc.M110.167155
Jellinger KA (2009) Recent advances in our understanding of neurodegeneration. J Neural Transm 116(9):1111–1162. https://doi.org/10.1007/s00702-009-0240-y
Jin HS, Sõber S, Hong KW, Org E, Kim BY, Laan M, Jeong SY (2011) Age-dependent association of the polymorphisms in the mitochondria-shaping gene, OPA1, with blood pressure and hypertension in Korean population. Am J Hypertens 24(10):1127–1135. https://doi.org/10.1038/ajh.2011.131
Jones BL, Smith SM (2016) Calcium-sensing receptor: a key target for extracellular calcium signaling in neurons. Front Physiol 7:116. https://doi.org/10.3389/fphys.2016.00116
Joshi AU, Saw NL, Shamlo M, Mochly-Rosen D (2017) Drp1/Fis1 interaction mediates mitochondrial dysfunction, bioenergetic failure and cognitive decline in Alzheimer’s disease. Oncotarget 5(5):6128–6143. https://doi.org/10.18632/oncotarget.23640
Kageyama Y, Zhang Z, Roda R, Fukaya M, Wakabayashi J, Wakabayashi N, Sesaki H (2012) Mitochondrial division ensures the survival of postmitotic neurons by suppressing oxidative damage. J Cell Biol 197(4):535–551. https://doi.org/10.1083/jcb.201110034
Kageyama RM, Iijima M, Sesaki H (2015) PARK2/Parkin becomes critical when DNM1L/Drp1 is absent. Autophagy 11(3):573–574. https://doi.org/10.1080/15548627.2015.1017193
Kandimalla R, Reddy PH (2016) Multiple faces of dynamin-related protein 1 and its role in Alzheimer’s disease pathogenesis. Biochim Biophys Acta 4:814–828. https://doi.org/10.1016/j.bbadis.2015.12.018
Kanfer G, Peterka M, Arzhanik VK, Drobyshev AL, Ataullakhanov FI, Volkov VA, Kornmann B (2017) CENP-F couples cargo to growing and shortening microtubule ends. Mol Biol Cell 28(18):2400–2409. https://doi.org/10.1091/mbc.E16-11-0756
Kann O, Kovacs R (2007) Mitochondria and neuronal activity. AJP 292(2):C641–C657. https://doi.org/10.1152/ajpcell.00222.2006
Kaplan A, Kent CB, Charron F, Fournier AE (2014) Switching responses: spatial and temporal regulators of axon guidance. Mol Neurobiol 49(2):1077–1086. https://doi.org/10.1007/s12035-013-8582-8
Karbowski M, Neutzner A, Youle RJ (2007) The mitochondrial E3 ubiquitin ligase MARCH5 is required for Drp1 dependent mitochondrial division. J Cell Biol 178(1):71–84. https://doi.org/10.1083/jcb.200611064
Khacho M, Slack RS (2018) Mitochondrial dynamics in the regulation of neurogenesis: from development to the adult brain. Dev Dyn 247(1):47–52. https://doi.org/10.1002/dvdy.24538
Kim JE, Kang TC (2017) p47Phox/CDK5/DRP1-mediated mitochondrial fission evokes PV cell degeneration in the rat dentate gyrus following status epilepticus. Front Cell Neur 11(September):1–13. https://doi.org/10.3389/fncel.2017.00267
Kim DI, Lee KH, Gabr AA, Choi GE, Kim JS, Ko SH, Han HJ (2016) Aβ-Induced Drp1 phosphorylation through Akt activation promotes excessive mitochondrial fission leading to neuronal apoptosis. Biochim Biophys Acta 1863(11):2820–2834. https://doi.org/10.1016/j.bbamcr.2016.09.003
Kim J, Moody JP, Edgerly CK, Bordiuk OL, Cormier K, Smith K, Beal MF, Ferrante RJ (2010a) Mitochondrial loss, dysfunction and altered dynamics in Huntington’s disease. Hum Mol Genet 19(20):3919–3935. https://doi.org/10.1093/hmg/ddq306
Kim JJ, Lee SB, Park JK, Yoo YD (2010b) TNF-α-induced ROS production triggering apoptosis is directly linked to Romo1 and Bcl-XL. Cell Death Differ 17(9):1420–1434. https://doi.org/10.1038/cdd.2010.19
Knott AB, Perkins G, Schwarzenbacher R, Bossy-Wetzel E (2008) Mitochondrial fragmentation in neurodegeneration. Nat Rev Neurosci 9(7):505–518. https://doi.org/10.1038/nrn2417
Komuro Y, Galas L, Lebon A, Raoult E, Fahrion JK, Tilot A, Kumada T, Ohno N, Vaudry D, Komuro H (2015) The role of calcium and cyclic nucleotide signaling in cerebellar granule cell migration under normal and pathological conditions. Dev Neurobiol 75(4):369–387. https://doi.org/10.1002/dneu.22219
Kuruva CS, Manczak M, Yin X, Ogunmokun G, Reddy AP, Reddy PH (2017) Aqua-soluble DDQ reduces the levels of Drp1 and Aβ and inhibits abnormal interactions between Aβ and Drp1 and protects Alzheimer’s disease neurons from Aβ- and Drp1-induced mitochondrial and synaptic toxicities. Hum Mol Genet 26(17):3375–3395. https://doi.org/10.1093/hmg/ddx226
Kuznetsov AV, Hermann M, Saks V, Hengster P, Margreiter R (2009) The cell-type specificity of mitochondrial dynamics. Int J Biochem Cell Biol 41(10):1928–1939. https://doi.org/10.1016/j.biocel.2009.03.007
Labrousse AM, Zappaterra MD, Rube DA, Bliek AM, Bliek AM, Bliek AM (1999) C. elegans dynamin-related protein DRP-1 controls severing of the mitochondrial outer membrane. Mol Cell 4(5):815–826. https://doi.org/10.1016/S1097-2765(00)80391-3
Lackner LL (2014) Shaping the dynamic mitochondrial network. BMC Biol 12(1):35. https://doi.org/10.1186/1741-7007-12-35
Le Belle JE, Orozco NM, Paucar AA, Saxe JP, Mottahedeh J, Pyle AD, Kornblum HI (2011) Proliferative neural stem cells have high endogenous ROS levels that regulate self-renewal and neurogenesis in a PI3K/Akt-dependant manner. Cell Stem Cell 8(1):59–71. https://doi.org/10.1016/j.stem.2010.11.028
Leboucher GP, Tsai YC, Yang M, Shaw KC, Zhou M, Veenstra TD, Weissman AM (2012) Stress-induced phosphorylation and proteasomal degradation of mitofusin 2 facilitates mitochondrial fragmentation and apoptosis. Mol Cell 47(4):547–557. https://doi.org/10.1016/j.molcel.2012.05.041
Lee H, Yoon Y (2016) Mitochondrial fission and fusion. Biochem Soc Trans 44(6):1725–1735. https://doi.org/10.1042/BST20160129
Lee SB, Kim JJ, Kim TW, Kim BS, Lee MS, Do Yoo Y (2010) Serum deprivation-induced reactive oxygen species production is mediated by Romo1. Apoptosis 15(2):204–218. https://doi.org/10.1007/s10495-009-0411-1
Liguori M, La Russa A, Manna I, Andreoli V, Caracciolo M, Spadafora P, Cittadella R, Quattrone A (2008) A phenotypic variation of dominant optic atrophy and deafness (ADOAD) due to a novel OPA1 mutation. J Neurol 255(1):127–129. https://doi.org/10.1007/s00415-008-0571-x
Mailloux RJ, Jin X, Willmore WG (2013) Redox regulation of mitochondrial function with emphasis on cysteine oxidation reactions. Redox Biol 19(2):123–139. https://doi.org/10.1016/j.redox.2013.12.011
Manczak M, Sesaki H, Kageyama Y, Reddy PH (2012) Dynamin-related protein 1 heterozygote knockout mice do not have synaptic and mitochondrial deficiencies. BBA Mol Basis Dis 1822(6):862–874. https://doi.org/10.1016/j.bbadis.2012.02.017
Manczak M, Kandimalla R, Fry D, Sesaki H, Reddy P (2016) Protective effects of reduced dynamin-related protein 1 against amyloid beta-induced mitochondrial dysfunction and synaptic damage in Alzheimer’s disease. Hum Mol Gen 25(23):5148–5166. https://doi.org/10.1093/hmg/ddw330
Manczak M, Kandimalla R, Yin X, Reddy PH (2018) Hippocampal mutant APP and amyloid beta-induced cognitive decline, dendritic spine loss, defective autophagy, mitophagy and mitochondrial abnormalities in a mouse model of Alzheimer’s disease. Hum Mol Genet 27(8):1332–1342. https://doi.org/10.1093/hmg/ddy042
Martín-Maestro P, Gargini R, García E, Perry G, Avila J, García-Escudero V (2017) Slower dynamics and aged mitochondria in sporadic Alzheimer’s disease. Oxid Med Cell Longev 2017:9302761. https://doi.org/10.1155/2017/9302761
Martorell-Riera A, Segarra-Mondejar M, Munoz JP, Ginet V, Olloquequi J, Perez-Clausell J, Soriano FX (2014) Mfn2 downregulation in excitotoxicity causes mitochondrial dysfunction and delayed neuronal death. EMBO Journal 33(20):2388–2407. https://doi.org/10.15252/embj.201488327
Mears JA, Lackner LL, Fang S, Ingerman E, Nunnari J, Hinshaw JE (2011) Conformational changes in Dnm1 support a contractile mechanism for mitochondrial fission. Nat Struct Mol Biol 18(1):20–26. https://doi.org/10.1038/nsmb.1949
Millet AM, Bertholet AM, Daloyau M, Reynier P, Galinier A, Devin A, Davezac N (2016) Loss of functional OPA1 unbalances redox state: implications in dominant optic atrophy pathogenesis. Ann Clin Transl Neurol 3(6):408–421. https://doi.org/10.1002/acn3.305
Mironov SL (2009) Complexity of mitochondrial dynamics in neurons and its control by ADP produced during synaptic activity. Int J Biochem Cell Biol 41(10):2005–2014. https://doi.org/10.1016/j.biocel.2009.04.009
Mozdy AD, Shaw JM (2003) A fuzzy mitochondrial fusion apparatus comes into focus. Nat Rev Mol Cell Biol 4(6):468–478. https://doi.org/10.1038/nrm1125
Murphy MP (2009) How mitochondria produce reactive oxygen species. Biochem J 417(1):1–13. https://doi.org/10.1042/BJ20081386
Nakamura N, Kimura Y, Tokuda M, Honda S, Hirose S (2006) MARCH-V is a novel mitofusin 2- and Drp1-binding protein able to change mitochondrial morphology. EMBO Rep 7(10):1019–1022. https://doi.org/10.1038/sj.embor.7400790
Nayernia Z, Jaquet V, Krause KH (2014) New insights on NOX enzymes in the central nervous system. Antioxid Redox Signal 20(17):2815–2837. https://doi.org/10.1089/ars.2013.5703
Norton M, Cheuk-Him A, Baird S, Dumoulin A, Shutt T, Mah N, Screaton RA (2014) ROMO1 is an essential redox-dependent regulator of mitochondrial dynamics. Sci Signal 7(310):ra10 http://doi.org/10.1126/scisignal.2004374
Olguín-Albuerne M, Morán J (2015) ROS produced by NOX2 controls in vitro development of cerebellar granule neurons development. ASN Neuro 7(2):1–28. https://doi.org/10.1177/1759091415578712
Ordonez DG, Lee MK, Feany MB (2017) α-synuclein induces mitochondrial dysfunction through spectrin and the actin cytoskeleton. Neuron 97(1):108–124.e6. https://doi.org/10.1016/j.neuron.2017.11.036
Otera H, Mihara K (2011) Molecular mechanisms and physiologic functions of mitochondrial dynamics. J Biochem 149(3):241–251
Palmer CS, Osellame LD, Laine D, Koutsopoulos OS, Frazier AE, Ryan MT (2011) MiD49 and MiD51, new components of the mitochondrial fission machinery. EMBO Rep 12(6):565–573. https://doi.org/10.1038/embor.2011.54
Pareyson D, Saveri P, Sagnelli A, Piscosquito G (2015) Mitochondrial dynamics and inherited peripheral nerve diseases. Neurosci Lett 596:66–77. https://doi.org/10.1016/j.neulet.2015.04.001
Park S, Yang JS, Jang SK, Kim S (2009) Construction of functional interaction networks through consensus localization predictions of the human proteome. J Proteome Res 8(7):3367–3376. https://doi.org/10.1021/pr900018z
Pernas L, Scorrano L (2016) Mito-morphosis: mitochondrial fusion, fission, and cristae remodeling as key mediators of cellular function. Annu Rev Physiol 78(1):505–531. https://doi.org/10.1146/annurev-physiol-021115-105011
Phaniendra A, Jestadi DB, Periyasamy L (2015) Free radicals: properties, sources, targets, and their implication in various diseases. IJCB 30(1):11–26. https://doi.org/10.1007/s12291-014-0446-0
Piras S, Furfaro AL, Domenicotti C, Traverso N, Marinari UM, Pronzato MA, Nitti M (2016) RAGE expression and ROS generation in neurons: differentiation versus damage. Oxid Med Cell Longev 2016:9348651. https://doi.org/10.1155/2016/9348651
Prudent J, Zunino R, Suyiura A, Mattle S, Shore GC, McBrite H (2015) MAPL SUMOylation of Drp1 stabilizes and ER/mitochondrial platform required for cell death. Mol Cell 59(6):941–955. https://doi.org/10.1016/j.molcel.2015.08.001
Purnell PR, Fox HS (2013) Autophagy-mediated turnover of dynamin-related protein 1. BMC Neurosci 14:86. https://doi.org/10.1186/1471-2202-14-86
Reddy PH (2011) Abnormal tau, mitochondrial dysfunction, impaired axonal transport of mitochondria, and synaptic deprivation in Alzheimer’s disease. Brain Res 1415:136–148
Reddy PH, Shirendeb UP (2012) Mutant huntingtin, abnormal mitochondrial dynamics, defective axonal transport of mitochondria, and selective synaptic degeneration in Huntington’s disease. BBA 1822(2):101–110. https://doi.org/10.1016/j.bbadis.2011.10.016
Rezin GT, Amboni G, Zugno AI, Quevedo J, Streck EL (2009) Mitochondrial dysfunction and psychiatric disorders. Neurochem Res 34(6):1021–1029. https://doi.org/10.1007/s11064-008-9865-8
Rolfe DF, Brown GC (1997) Cellular energy utilization and molecular origin of standard metabolic rate in mammals. Physiol Rev 77(3):731–758. https://doi.org/10.1152/physrev.1997.77.3.731
Rubegni A, Pisano T, Bacci G, Tessa A, Battini R, Procopio E, Giglio S, Pasquariello R, Santorelli FM, Guerrini R, Nesti C (2017) Leigh-like neuroimaging features associated with new biallelic mutations in OPA1. Eur J Paediatr Neurol 21(4):671–677. https://doi.org/10.1016/j.ejpn.2017.04.004
Ryan JJ, Marsboom G, Archer SL (2013) Rodent models of group 1 pulmonary hypertension. Handb Exp Pharmacol 218:105–149. https://doi.org/10.1007/978-3-642-38664-0_5
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(4):200–210. https://doi.org/10.1016/j.tibs.2015.02.003
Santel A, Frank S (2008) Shaping mitochondria: the complex posttranslational regulation of the mitochondrial fission protein DRP1. IUBMB Life 60(7):448–455. https://doi.org/10.1002/iub.71
Santel A, Frank S, Gaume B, Herrler M, Youle RJ, Fuller M (2003) Mitofusin-1 protein is a generally expressed mediator of mitochondrial fusion in mammalian cells. J Cell Sci 116(13):2763–2774. https://doi.org/10.1242/jcs.00479
Schild AM, Ristau T, Fricke J, Neugebauer A, Kirchhof B, Sadda SR, Liakopoulos S (2013) SDOCT thickness measurements of various retinal layers in patients with autosomal dominant optic atrophy due to OPA1 mutations. Biomed Res Int 2013:121398
Schwarz TL (2013) Mitochondrial trafficking in neurons. Cold Spring Harb Perspect Biol. https://doi.org/10.1101/cshperspect.a011304
Seirafi M, Kozlov G, Gehring K (2015) Parkin structure and function. FEBS J 282(11):2076–2088. https://doi.org/10.1111/febs.13249
Sesaki H, Adachi Y, Kageyama Y, Itoh K, Iijima M (2014) In vivo functions of Drp1: lessons learned from yeast genetics and mouse knockouts. BBA Mol Basis Dis 1842(8):1179–1185. https://doi.org/10.1016/j.bbadis.2013.11.024
Sharp WW, Fang YH, Han M, Zhang HJ, Hong Z, Banathy A, Morrow E, Ryan JJ, Archer SL (2014) Dynamin-related protein 1 (Drp1)-mediated diastolic dysfunction in myocardial ischemia-reperfusion injury: therapeutic benefits of Drp1 inhibition to reduce mitochondrial fission. FASEB J 28(1):316–326. https://doi.org/10.1096/fj.12-226225
Sheng ZH, Cai Q (2012) Mitochondrial transport in neurons: impact on synaptic homeostasis and neurodegeneration. Nat Rev Neurosci 13(2):77–93. https://doi.org/10.1038/nrn3156
Shields LY, Kim H, Zhu L, Haddad D, Berthet A, Pathak D, Nakamura K (2015) Dynamin-related protein 1 is required for normal mitochondrial bioenergetic and synaptic function in CA1 hippocampal neurons. Cell Death Dis 6(4):e1725. https://doi.org/10.1038/cddis.2015.94
Shirendeb UP, Calkins MJ, Manczak M, Anekonda V, Dufour B, McBride JL, Mao P, Reddy PH (2012) Mutant huntingtin’s interaction with mitochondrial protein Drp1 impairs mitochondrial biogenesis and causes defective axonal transport and synaptic degeneration in Huntington’s disease. Hum Mol Genet 21(2):406–420. https://doi.org/10.1093/hmg/ddr475
Shutt T, Geoffrion M, Milne R, McBride HM (2012) The intracellular redox state is a core determinant of mitochondrial fusion. EMBO Rep 13(10):909–915. https://doi.org/10.1038/embor.2012.128
Song Z, Chen H, Fiket M, Alexander C, Chan DC (2007) OPA1 processing controls mitochondrial fusion and is regulated by mRNA splicing, membrane potential, and Yme1L. J Cell Biol 178(5):749–755. https://doi.org/10.1083/jcb.200704110
Song W, Chen J, Petrilli A, Liot G, Klinglmayr E, Poquiz P, Bossy-wetzel E (2011) Mutant huntingtin binds the mitochondrial fission gtpase Drp1 and increases its enzymatic activty. Nat Med 17(3):377–382. https://doi.org/10.1038/nm.2313
Taguchi N, Ishihara N, Jokufu A, Oka T, Mihara K (2007) Mitotic phosphorylation of dynamin- related GTPase participates in mitochondrial fission. J Biol Chem 282:11521–11529. https://doi.org/10.1074/jbc.M607279200
Twig G, Elorza A, Molina JA, Mohamed H, Wikstrom JD, Walzer G, Shirihai OS (2008) Fission and selective fusion govern mitochondrial segregation and elimination by autophagy. EMBO 27(2):433–446. https://doi.org/10.1038/sj.emboj.7601963
Wakabayashi J, Zhang Z, Wakabayashi N, Tamura Y, Fukaya M, Kensler TW, Sesaki H (2009) The dynamin-related GTPase Drp1 is required for embryonic and brain development in mice. J Cell Biol 186(6):805–816. https://doi.org/10.1083/jcb.200903065
Wang DB, Garden GA, Kinoshita C, Wyles C, Babazadeh N, Sopher B, Kinoshita Y, Morrison RS (2013) Changes in mitochondrial length and neuronal death. J Neurosci 33(4):1357–1365. https://doi.org/10.1523/JNEUROSCI.3365-12.2013
Wang W, Zhang F, Li L, Tang F, Siedlak SL, Fujioka H, Wang X (2015) MFN2 couples glutamate excitotoxicity and mitochondrial dysfunction in motor neurons. J Biol Chem 290(1):168–182. https://doi.org/10.1074/jbc.M114.617167
Wappler EA, Institoris A, Dutta S, Katakam VG, Busija DW (2013) Mitochondrial dynamics associated with oxygen-glucose deprivation in rat primary neuronal cultures. PLoS ONE 8(5):e63206. https://doi.org/10.1371/journal.pone.0063206
Waterham HR, Koster J, van Roermund CT, Mooyer PA, Wanders R, Leonard JV (2007) A lethal defect of mitochondrial and peroxisomal fission. N Engl J Med 356(17):1736–1741. https://doi.org/10.1056/NEJMoa064436
Westermann B (2010) Mitochondrial fusion and fission in cell life and death. Nat Rev Mol Cell Biol 11(12):872–884. https://doi.org/10.1038/nrm3013
Westernmann B (2012) Bioenergetic role of mitochondrial fusion and fission. BBA 1817(10):1833–1838. https://doi.org/10.1016/j.bbabio.2012.02.033
Willems PH, Rossignol R, Dieteren CE, Murphy MP, Koopman WJ (2015) Redox homeostasis and mitochondrial dynamics. Cell Metab 422(2):207–218. https://doi.org/10.1016/j.cmet.2015.06.006
Wilson TJ, Slupe AM, Strack S (2013) Cell signaling and mitochondrial dynamics: implications for neuronal function and neurodegenerative disease. Neurobiol Dis 51:13–26. https://doi.org/10.1016/j.nbd.2012.01.009
Wu Q, Gao C, Wang H, Zhang X, Li Q, Gu Z, Shi X, Cui Y, Wang T, Chen X, Wang X, Luo C, Tao L (2018) Mdivi-1 alleviates blood-brain barrier disruption and cell death in experimental traumatic brain injury by mitigating autophagy dysfunction and mitophagy activation. Int J Biochem Cell Biol 22(94):44–55. https://doi.org/10.1016/j.biocel.2017.11.007
Youle RJ, van der Bliek AM (2012) Mitochondrial fission, fusion, and stress. Science 337:1062–1065. https://doi.org/10.1126/science.1219855
Yu T, Sheu SS, Robotham JL, Yoon Y (2009) Mitochondrial fission mediates high glucose-induced cell death through elevated production of reactive oxygen species. Cardiovasc Res 79(2):341–351. https://doi.org/10.1093/cvr/cvn104
Yu-Wai-Man P, Chinnery PF (2011) Reply: spastic paraplegia in ‘dominant optic atrophy plus’ phenotype due to OPA1 mutation. Brain 134(11):e196
Zhang Z, Liu L, Jiang X, Zhai S, Xing D (2016) The essential role of Drp1 and its regulation by S-Nitrosylation of parkin in dopaminergic neurodegeneration: implications for Parkinson’s disease. Antioxid Redox Signal 25(11):609–622. https://doi.org/10.1089/ars.2016.6634
Zhang J, Liu X, Liang X, Lu Y, Zhu L, Fu R, Ji Y, Fan W, Chen J, Lin B, Yuan Y, Jiang P, Zhou X, Guan MX (2017) A novel ADOA-associated OPA1 mutation alters the mitochondrial function, membrane potential, ROS production and apoptosis. Sci Rep 7(1):5704. https://doi.org/10.1038/s41598-017-05571-y
Zhao Q, Wang S, Li Y, Wang P, Li S, Guo Y, Yao R (2013) The role of the mitochondrial calcium uniporter in cerebral ischemia/reperfusion injury in rats involves regulation of mitochondrial energy metabolism. Mol Med Rep 7(4):1073–1080. https://doi.org/10.3892/mmr.2013.1321
Zhao F, Wang W, Wang C, Siedlak SL, Fujioka H, Tang B, Zhu X (2017) Mfn2 protects dopaminergic neurons exposed to paraquat both in vitro and in vivo: implications for idiopathic Parkinson’s disease. Biochim Biophys Acta 1863(6):1359–1370. https://doi.org/10.1016/j.cell.2006.06.025
Zhou L, Zhang Q, Zhang P, Sun L, Peng C, Yuan Z, Cheng J (2017) c-Abl-mediated Drp1 phosphorylation promotes oxidative stress-induced mitochondrial fragmentation and neuronal cell death. Cell Death Dis 8(10):e3117. https://doi.org/10.1038/cddis.2017.524
Zhu PP, Patterson A, Stadler J, Seeburg DP, Sheng M, Blackstone C (2004) Intra- and intermolecular domain interactions of the C-terminal GTPase effector domain of the multimeric dynamin-like GTPase Drp1. J Biol Chem 279:5967–35974. https://doi.org/10.1155/2016/9348651
Züchner S, Mersiyanova IV, Muglia M, Bissar-Tadmouri N, Rochelle J, Dadali EL, Vance JM (2004) Mutations in the mitochondrial GTPase mitofusin 2 cause Charcot-Marie-Tooth neuropathy type 2A. Nat Gen 36(5):449–451. https://doi.org/10.1038/ng1341
Acknowledgements
The authors appreciate the contribution of Gabriela Gutierrez-Chávez for the elaboration of the figures. This study was supported by DGAPA-PAPIIT, UNAM (IN-210716), Fundación Miguel Alemán, México and CONACyT (285184).
Author information
Authors and Affiliations
Contributions
CC-C and DRH-E collected the information and wrote the manuscript with critical revision and comments by JM.
Corresponding author
Ethics declarations
Conflict of interest
The authors declare that there is no conflict of interests.
Rights and permissions
About this article
Cite this article
Cid-Castro, C., Hernández-Espinosa, D.R. & Morán, J. ROS as Regulators of Mitochondrial Dynamics in Neurons. Cell Mol Neurobiol 38, 995–1007 (2018). https://doi.org/10.1007/s10571-018-0584-7
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s10571-018-0584-7