Abstract
This chapter will cover the physiological role of autophagy at the organismal level. We will also address how dysfunction of autophagy is interconnected to ageing and associated degenerative diseases, like neurodegeneration and cancer.
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References
Aita VM, Liang XH, Murty VVVS et al (1999) Cloning and genomic organization of Beclin 1, a candidate tumor suppressor gene on chromosome 17q21. Genomics 59:59–65. doi:10.1006/geno.1999.5851
Al Rawi S, Louvet-Vallée S, Djeddi A, et al (2011) Postfertilization autophagy of sperm organelles prevents paternal mitochondrial DNA transmission. Science (New York, NY) 334:1144–1147. doi:10.1126/science.1211878
Apfeld J, O’Connor G, McDonagh T et al (2004) The AMP-activated protein kinase AAK-2 links energy levels and insulin-like signals to lifespan in C. elegans. Genes Dev 18:3004–3009. doi:10.1101/gad.1255404
Baerga R, Zhang Y, chen P-H et al (2009) Targeted deletion of autophagy-related 5 (Atg5) impairs adipogenesis in a cellular model and in mice. Autophagy 5:1118–1130
Barmada SJ, Serio A, Arjun A et al (2014) Autophagy induction enhances TDP43 turnover and survival in neuronal ALS models. Nat Chem Biol 10:677–685. doi:10.1038/nchembio.1563
Baumer D, Talbot K, Turner MR (2014) Advances in motor neurone disease. J R Soc Med 107:14–21. doi:10.1177/0141076813511451
Bergamini E (2005) Targets for antiageing drugs. Expert Opin Ther Targets 9:77–82. doi:10.1517/14728222.9.1.77
Berger Z, Davies JE, Luo S et al (2006) Deleterious and protective properties of an aggregate-prone protein with a polyalanine expansion. Hum Mol Genet 15:453–465. doi:10.1093/hmg/ddi460
Bjorkoy G (2005) p62/SQSTM1 forms protein aggregates degraded by autophagy and has a protective effect on huntingtin-induced cell death. J Cell Biol 171:603–614. doi:10.1083/jcb.200507002
Boland B, Kumar A, Lee S et al (2008) Autophagy induction and autophagosome clearance in neurons: relationship to autophagic pathology in Alzheimer’s disease. J Neurosci Off J Soc Neurosci 28:6926–6937. doi:10.1523/JNEUROSCI.0800-08.2008
Cadwell K, Patel KK, Maloney NS et al (2010) Virus-plus-susceptibility gene interaction determines Crohn’s disease gene Atg16L1 phenotypes in intestine. Cell 141:1135–1145. doi:10.1016/j.cell.2010.05.009 PubMed—NCBI
Cai X, Chiu Y-H, Chen ZJ (2014) The cGAS-cGAMP-STING pathway of cytosolic DNA sensing and signaling. Mol Cell 54:289–296 PubMed—NCBI
Castillo K, Nassif M, Valenzuela V et al (2014) Trehalose delays the progression of amyotrophic lateral sclerosis by enhancing autophagy in motoneurons. Autophagy 9:1308–1320. doi:10.4161/auto.25188
Cattaneo E, Zuccato C, Tartari M (2005) Normal huntingtin function: an alternative approach to Huntington’s disease. Nat Rev Neurosci 6:919–930. doi:10.1038/nrn1806
Chen M, Hong MJ, Sun H et al (2014) Essential role for autophagy in the maintenance of immunological memory against influenza infection. Nat Med 20:503–510. doi:10.1038/nm.3521
Chen M, Kodali S, Jang A, et al (2015) Requirement for autophagy in the long-term persistence but not initial formation of memory B cells. J Immunol (Baltimore, Md: 1950) 194:2607–2615. doi:10.4049/jimmunol.1403001
Cliby W, Ritland S, Hartmann L et al (1993) Human epithelial ovarian cancer allelotype. Cancer Res 53:2393–2398
Decressac M, Mattsson B, Weikop P et al (2013) TFEB-mediated autophagy rescues midbrain dopamine neurons from -synuclein toxicity. Proc Nat Acad Sci USA 110:E1817–E1826. doi:10.1073/pnas.1305623110
Degenhardt K, Mathew R, Beaudoin B et al (2006) Autophagy promotes tumor cell survival and restricts necrosis, inflammation, and tumorigenesis. Cancer Cell 10:51–64. doi:10.1016/j.ccr.2006.06.001
Del Roso A (2003) Ageing-related changes in the in vivo function of rat liver macroautophagy and proteolysis. Exp Gerontol 38:519–527. doi:10.1016/s0531-5565(03)00002-0
Diwan A, Koesters AG, Odley AM et al (2007) Unrestrained erythroblast development in Nix-/- mice reveals a mechanism for apoptotic modulation of erythropoiesis. Proc Nat Acad Sci USA 104:6794–6799. doi:10.1073/pnas.0610666104
Donati A, Cavallini G, Paradiso C et al (2001) Age-Related changes in the regulation of autophagic proteolysis in rat isolated hepatocytes. J Gerontol Ser A Biol Sci Med Sci 56:B288–B293. doi:10.1093/gerona/56.7.b288
Dragatsis I, Levine MS, Zeitlin S (2000) Inactivation of Hdh in the brain and testis results in progressive neurodegeneration and sterility in mice. Nat Genet 26:300–306. doi:10.1038/81593
Dupont N, Jiang S, Pilli M et al (2011) Autophagy-based unconventional secretory pathway for extracellular delivery of IL-1β. EMBO J 30:4701–4711. doi:10.1038/emboj.2011.398
Ebato C, Uchida T, Arakawa M et al (2008) Autophagy is important in islet homeostasis and compensatory increase of beta cell mass in response to high-fat diet. Cell Metab 8:325–332. doi:10.1016/j.cmet.2008.08.009
Eccles DM, Russell SE, Haites NE et al (1992) Early loss of heterozygosity on 17q in ovarian cancer. The Abe Ovarian Cancer Genetics Group. Oncogene 7:2069–2072
Egan DF, Shackelford DB, Mihaylova MM et al (2011) Phosphorylation of ULK1 (hATG1) by AMP-activated protein kinase connects energy sensing to mitophagy. Science 331:456–461. doi:10.1126/science.1196371 PubMed—NCBI
Eisenberg T, Knauer H, Schauer A et al (2009) Induction of autophagy by spermidine promotes longevity. Nat Cell Biol 11:1305–1314. doi:10.1038/ncb1975
Fecto F (2011) SQSTM1 Mutations in Familial and Sporadic Amyotrophic Lateral Sclerosis. Arch Neurol 68:1440. doi:10.1001/archneurol.2011.250
Frake RA, Ricketts T, Menzies FM, Rubinsztein DC (2015) Autophagy and neurodegeneration. J clin Invest 125:65–74. doi:10.1172/JCI73944
Friedman DB, Johnson TE (1988) A mutation in the age-1 gene in Caenorhabditis elegans lengthens life and reduces hermaphrodite fertility. Genetics 118:75–86
Fujita N, Morita E, Itoh T et al (2013) Recruitment of the autophagic machinery to endosomes during infection is mediated by ubiquitin. J Cell Biol 203:115–128. doi:10.1083/jcb.201304188
Futreal PA, Söderkvist P, Marks JR et al (1992) Detection of frequent allelic loss on proximal chromosome 17q in sporadic breast carcinoma using microsatellite length polymorphisms. Cancer Res 52:2624–2627
Gao X, Zacharek A, Salkowski A et al (1995) Loss of heterozygosity of the BRCA1 and other loci on chromosome 17q in human prostate cancer. Cancer Res 55:1002–1005
Geisler S, Holmström KM, Skujat D et al (2010) PINK1/Parkin-mediated mitophagy is dependent on VDAC1 and p62/SQSTM1. Nat Cell Biol 12:119–131. doi:10.1038/ncb2012
Gelino S, Hansen M (2012) Autophagy - An Emerging Anti-Aging Mechanism
Gems D, Partridge L (2013) Genetics of longevity in model organisms: debates and paradigm shifts. Annu Rev Physiol 75:621–644. doi:10.1146/annurev-physiol-030212-183712
Goate A, Chartier-Harlin M-C, Mullan M et al (1991) Segregation of a missense mutation in the amyloid precursor protein gene with familial Alzheimer’s disease. Nature 349:704–706. doi:10.1038/349704a0
Gronowicz G, Swift H, Steck TL (1984) Maturation of the reticulocyte in vitro. J Cell Sci 71:177–197
Guo JY, Chen HY, Mathew R et al (2011) Activated Ras requires autophagy to maintain oxidative metabolism and tumorigenesis. Genes Dev 25:460–470. doi:10.1101/gad.2016311 PubMed—NCBI
Guo JY, Karsli-Uzunbas G, Mathew R et al (2013) Autophagy suppresses progression of K-ras-induced lung tumors to oncocytomas and maintains lipid homeostasis. Genes Dev 27:1447–1461. doi:10.1101/gad.219642.113
Gutierrez MG, Master SS, Singh SB et al (2004) Autophagy is a defense mechanism inhibiting BCG and mycobacterium tuberculosis survival in infected macrophages. Cell 119:753–766. doi:10.1016/j.cell.2004.11.038
Hampe J, Franke A, Rosenstiel P et al (2007) A genome-wide association scan of nonsynonymous SNPs identifies a susceptibility variant for Crohn disease in ATG16L1. Nat Genet 39:207–211. doi:10.1038/ng1954
Hansen M, Chandra A, Mitic LL et al (2008) A role for autophagy in the extension of lifespan by dietary restriction in C. elegans. PLoS Genet 4:e24. doi:10.1371/journal.pgen.0040024
Hara T, Nakamura K, Matsui M et al (2006) Suppression of basal autophagy in neural cells causes neurodegenerative disease in mice. Nature 441:885–889. doi:10.1038/nature04724
Harjes P, Wanker EE (2003) The hunt for huntingtin function: interaction partners tell many different stories. Trends Biochem Sci 28:425–433. doi:10.1016/S0968-0004(03)00168-3
Hartleben B, Gödel M, Meyer-Schwesinger C et al (2010) Autophagy influences glomerular disease susceptibility and maintains podocyte homeostasis in aging mice. J Clin Invest 120:1084–1096. doi:10.1172/JCI39492
Hattori N, Kitada T, Matsumine H et al (1998) Molecular genetic analysis of a novel Parkin gene in Japanese families with autosomal recessive juvenile parkinsonism: evidence for variable homozygous deletions in the Parkin gene in affected individuals. Ann Neurol 44:935–941. doi:10.1002/ana.410440612
He C, Bassik MC, Moresi V, et al (2012) Exercise-induced BCL2-regulated autophagy is required for muscle glucose homeostasis. Nature Adv 511–515. doi:10.1038/nature10758
Heng MY, Duong DK, Albin RL et al (2010) Early autophagic response in a novel knock-in model of Huntington disease. Hum Mol Genet 19:3702–3720. doi:10.1093/hmg/ddq285
Hetz C, Thielen P, Matus S et al (2009) XBP-1 deficiency in the nervous system protects against amyotrophic lateral sclerosis by increasing autophagy. Genes Dev 23:2294–2306. doi:10.1101/gad.1830709
Heynen MJ, Tricot G, Verwilghen RL (1985) Autophagy of mitochondria in rat bone marrow erythroid cells. Relation to nuclear extrusion. Cell Tissue Res 239:235–239
Hirano M, Nakamura Y, Saigoh K et al (2013) Mutations in the gene encoding p62 in Japanese patients with amyotrophic lateral sclerosis. Neurology 80:458–463. doi:10.1212/WNL.0b013e31827f0fe5
Holtzman DM, John CM, Goate A (2011) Alzheimer’s disease: the challenge of the second century. Sci Trans Med 3:77sr1–77sr1. doi:10.1126/scitranslmed.3002369
Huang J, Brumell JH (2014) Bacteria-autophagy interplay: a battle for survival. Nat Rev Microbiol 12:101–114. doi:10.1038/nrmicro3160
Huo Y, Cai H, Teplova I et al (2013) Autophagy opposes p53-mediated tumor barrier to facilitate tumorigenesis in a model of PALB2-associated hereditary breast cancer. Cancer Discov 3:894–907. doi:10.1158/2159-8290.CD-13-0011 PubMed—NCBI
Inoue K, Rispoli J, Kaphzan H et al (2012) Macroautophagy deficiency mediates age-dependent neurodegeneration through a phospho-tau pathway. Mol Neurodegener 7:48. doi:10.1186/1750-1326-7-48
Iwata A, Christianson JC, Bucci M et al (2005) Increased susceptibility of cytoplasmic over nuclear polyglutamine aggregates to autophagic degradation. Proc Natl Acad Sci USA 102:13135–13140. doi:10.1073/pnas.0505801102
Jankovic J (2008) Parkinson’s disease: clinical features and diagnosis. J Neurol Neurosurg Psychiatr 79:368–376. doi:10.1136/jnnp.2007.131045
Jia W, Pua HH, Li QJ, He YW (2011) Autophagy regulates endoplasmic reticulum homeostasis and calcium mobilization in T lymphocytes. J Immunol 186:1564–1574. doi:10.4049/jimmunol.1001822 PubMed—NCBI
Jiang T, Yu J-T, Zhu X-C et al (2014) Temsirolimus promotes autophagic clearance of amyloid-β and provides protective effects in cellular and animal models of Alzheimer’s disease. Pharmacol Res 81:54–63. doi:10.1016/j.phrs.2014.02.008
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. doi:10.4161/auto.26122
Johansen T, Lamark T (2011) Selective autophagy mediated by autophagic adapter proteins. Autophagy 7:279–296. doi:10.4161/auto.7.3.14487
Jounai N, Takeshita F, Kobiyama K et al (2007) The Atg5 Atg12 conjugate associates with innate antiviral immune responses. Proc Natl Acad Sci USA 104:14050–14055. doi:10.1073/pnas.0704014104
Juhasz G, Erdi B, Sass M, Neufeld TP (2007) Atg7-dependent autophagy promotes neuronal health, stress tolerance, and longevity but is dispensable for metamorphosis in Drosophila. Genes Dev 21:3061–3066. doi:10.1101/gad.1600707
Juhász G, Csikós G, Sinka R et al (2003) The Drosophila homolog of Aut1 is essential for autophagy and development. FEBS Lett 543:154–158. doi:10.1016/s0014-5793(03)00431-9
Jung HS, Chung KW, Won Kim J et al (2008) Loss of autophagy diminishes pancreatic β cell mass and function with resultant hyperglycemia. Cell Metab 8:318–324. doi:10.1016/j.cmet.2008.08.013
Kageyama S1, Omori H, Saitoh T, Sone T, Guan JL, Akira S, Imamoto F, Noda T, Yoshimori T. (2011) The LC3 recruitment mechanism is separate from Atg9L1-dependent membrane formation in the autophagic response against Salmonella. Mol Biol Cell. 1 Jul 2011, 22(13):2290–2300
Karantza-Wadsworth V, Patel S, Kravchuk O et al (2007) Autophagy mitigates metabolic stress and genome damage in mammary tumorigenesis. Genes Dev 21:1621–1635. doi:10.1101/gad.1565707
Kaushik S, Arias E, Kwon H et al (2012) Loss of autophagy in hypothalamic POMC neurons impairs lipolysis. EMBO Rep 13:258–265 PubMed—NCBI
Kegel KB, Kim M, Sapp E et al (2000) Huntingtin expression stimulates endosomal-lysosomal activity, endosome tubulation, and autophagy. J Neurosci Off J Soc Neurosci 20:7268–7278
Kent G, Minick OT, Volini FI, Orfei E (1966) Autophagic vacuoles in human red cells. Am J Pathol 48:831–857
Kenyon C, Chang J, Gensch E et al (1993) A C. elegans mutant that lives twice as long as wild type. Nature 366:461–464. doi:10.1038/366461a0
Khaminets A, Behl C, Dikic I (2016) Ubiquitin-dependent and independent signals in selective autophagy. Trends Cell Biol 26:6–16. doi:10.1016/j.tcb.2015.08.010 PubMed—NCBI
Kiriyama Y, Nochi H (2015) The function of autophagy in neurodegenerative diseases. IJMS 16:26797–26812. doi:10.3390/ijms161125990
Kirkwood TBL (2005) Understanding the odd science of aging. Cell 120:437–447. doi:10.1016/j.cell.2005.01.027
Kitada T, Asakawa S, Hattori N et al (1998) Mutations in the parkin gene cause autosomal recessive juvenile parkinsonism. Nature 392:605–608. doi:10.1038/33416
Komatsu M, Kurokawa H, Waguri S et al (2010) The selective autophagy substrate p62 activates the stress responsive transcription factor Nrf2 through inactivation of Keap1. Nat Cell Biol 12:213–223. doi:10.1038/ncb2021 PubMed—NCBI
Komatsu M, Waguri S, Chiba T et al (2006) Loss of autophagy in the central nervous system causes neurodegeneration in mice. Nature 441:880–884. doi:10.1038/nature04723
Komatsu M, Waguri S, Koike M et al (2007a) Homeostatic levels of p62 control cytoplasmic inclusion body formation in autophagy-deficient mice. Cell 131:1149–1163. doi:10.1016/j.cell.2007.10.035
Komatsu M, Waguri S, Koike M et al (2007b) Homeostatic levels of p62 control cytoplasmic inclusion body formation in autophagy-deficient mice. Cell 131:1149–1163. doi:10.1016/j.cell.2007.10.035
Komatsu M, Waguri S, Ueno T et al (2005) Impairment of starvation-induced and constitutive autophagy in Atg7-deficient mice. J Cell Biol 169:425–434. doi:10.1083/jcb.200412022
Konno H, Konno K, Barber GN (2013) Cyclic dinucleotides trigger ULK1 (ATG1) phosphorylation of STING to prevent sustained innate immune signaling. Cell 155:688–698. doi:10.1016/j.cell.2013.09.049
Korac J, Schaeffer V, Kovacevic I et al (2013) Ubiquitin-independent function of optineurin in autophagic clearance of protein aggregates. J Cell Sci 126:580–592. doi:10.1242/jcs.114926
Krüger U, Wang Y, Kumar S, Mandelkow E-M (2012) Autophagic degradation of tau in primary neurons and its enhancement by trehalose. Neurobiol Aging 33:2291–2305. doi:10.1016/j.neurobiolaging.2011.11.009
Kuma A, Hatano M, Matsui M et al (2004) The role of autophagy during the early neonatal starvation period. Nature 432:1032–1036. doi:10.1038/nature03029
Kundu M, Lindsten T, Yang C-Y, Wu J, Zhao F, Zhang J, Selak MA, Ney PA, Thompson CB (2008) Ulk1 plays a critical role in the autophagic clearance of mitochondria and ribosomes during reticulocyte maturation. Blood 112:1493–1502. doi:10.1182/blood-2008-02-137398
Lapierre LR, Gelino S, Meléndez A, Hansen M (2011) Autophagy and lipid metabolism coordinately modulate lifespan in germline-less C. elegans. Curr Biol CB 21:1507–1514. doi:10.1016/j.cub.2011.07.042
Lawrence MS, Stojanov P, Mermel CH et al (2014) Discovery and saturation analysis of cancer genes across 21 tumour types. Nature 505:495–501
Lazarou M, Sliter DA, Kane LA et al (2015) The ubiquitin kinase PINK1 recruits autophagy receptors to induce mitophagy. Nature 524:309–314. doi:10.1038/nature14893
Lee HK, Lund JM, Ramanathan B, Mizushima N (2007) Autophagy-dependent viral recognition by plasmacytoid dendritic cells. Science 315:1398–1401. doi:10.1126/science.1136880
Lee J-H, Yu WH, Kumar A et al (2010a) Lysosomal proteolysis and autophagy require presenilin 1 and are disrupted by Alzheimer-related PS1 mutations. Cell 141:1146–1158. doi:10.1016/j.cell.2010.05.008
Lee J-Y, Nagano Y, Taylor JP et al (2010b) Disease-causing mutations in parkin impair mitochondrial ubiquitination, aggregation, and HDAC6-dependent mitophagy. J Cell Biol 189:671–679. doi:10.1083/jcb.201001039
Levine B, Mizushima N, Virgin HW (2011) Autophagy in immunity and inflammation. Nature 469:323–335. doi:10.1038/nature09782
Levy-Lahad E, Wasco W, Poorkaj P et al (1995) Candidate gene for the chromosome 1 familial Alzheimer’s disease locus. Science 269:973–977. doi:10.1126/science.7638622
Li L, Zhang S, Zhang X et al (2013) Autophagy enhancer carbamazepine alleviates memory deficits and cerebral amyloid-β pathology in a mouse model of Alzheimer’s disease. Curr Alzheimer Res 10:433–441
Li L, Zhang X, Le W (2008) Altered macroautophagy in the spinal cord of SOD1 mutant mice. Autophagy 4:290–293
Li S-H, Li X-J (2004) Huntingtin–protein interactions and the pathogenesis of Huntington’s disease. Trends Genet 20:146–154. doi:10.1016/j.tig.2004.01.008
Liang C-C, Wang C, Peng X et al (2010) Neural-specific deletion of FIP200 Leads to cerebellar degeneration caused by increased neuronal death and axon degeneration. J Biol Chem 285:3499–3509. doi:10.1074/jbc.M109.072389
Liang Q, Seo GJ, Choi YJ et al (2014) Crosstalk between the cGAS DNA sensor and Beclin-1 autophagy protein shapes innate antimicrobial immune responses. Cell Host Microbe 15:228–238. doi:10.1016/j.chom.2014.01.009
Liang XH, Jackson S, Seaman M et al (1999) Induction of autophagy and inhibition of tumorigenesis by Beclin 1. Nature 402:672–676. doi:10.1038/45257
Liang XH, Kleeman LK, Jiang HH et al (1998) Protection against fatal Sindbis virus encephalitis by beclin, a novel Bcl-2-interacting protein. J Virol 72:8586–8596
Lionaki E, Markaki M, Tavernarakis N (2013) Autophagy and ageing: insights from invertebrate model organisms. Ageing Res Rev 12:413–428. doi:10.1016/j.arr.2012.05.001
Lipinski MM, Zheng B, Lu T et al (2010) Genome-wide analysis reveals mechanisms modulating autophagy in normal brain aging and in Alzheimer’s disease. Proc Natl Acad Sci USA 107:14164–14169. doi:10.1073/pnas.1009485107 PubMed—NCBI
Liu X, Klionsky DJ (2014) Autophagy and immunity. Wiley, Hoboken, NJ, USA
Lock R, Kenific CM, Leidal AM et al (2014) Autophagy-dependent production of secreted factors facilitates oncogenic RAS-driven invasion. Cancer Discov 4:466–479. doi:10.1158/2159-8290.CD-13-0841 PubMed—NCBI
Lock R, Roy S, Kenific CM et al (2011) Autophagy facilitates glycolysis during Ras-mediated oncogenic transformation. Mol Biol Cell 22:165–178. doi:10.1091/mbc.E10-06-0500 PubMed—NCBI
López-Otin C, Blasco MA, Partridge L et al (2013) The hallmarks of aging. Cell 153:1194–1217. doi:10.1016/j.cell.2013.05.039
Lu K, Psakhye I, Jentsch S (2014) Autophagic clearance of polyQ proteins mediated by ubiquitin-Atg8 adaptors of the conserved CUET protein family. Cell 158:549–563. doi:10.1016/j.cell.2014.05.048
Lupfer C, Thomas PG, Anand PK et al (2013) Receptor interacting protein kinase 2–mediated mitophagy regulates inflammasome activation during virus infection. Nat Immunol 14:480–488. doi:10.1038/ni.2563
Lücking CB, Abbas N, Dürr A et al (1998) Homozygous deletions in parkin gene in European and North African families with autosomal recessive juvenile parkinsonism. The European Consortium on Genetic Susceptibility in Parkinson“s Disease and the French Parkinson”s Disease Genetics Study Group. Lancet 352:1355–1356
Ma XH, Piao S, Wang D et al (2011) Measurements of tumor cell autophagy predict invasiveness, resistance to chemotherapy, and survival in melanoma. Clin Cancer Res Off J Am Assoc Cancer Res 17:3478–3489. doi:10.1158/1078-0432.CCR-10-2372
MacDonald ME, Ambrose CM, Duyao MP et al (1993) A novel gene containing a trinucleotide repeat that is expanded and unstable on Huntington’s disease chromosomes. Cell 72:971–983. doi:10.1016/0092-8674(93)90585-E
Madeo F, Zimmermann A, Maiuri MC, Kroemer G (2015) Essential role for autophagy in life span extension. J Clin Invest 125:85–93. doi:10.1172/JCI73946 PubMed—NCBI
Mah LY, Ryan KM (2012) Autophagy and cancer. Cold Spring Harb Perspect Biol 4:a008821–a008821. doi:10.1101/cshperspect.a008821 PubMed—NCBI
Mai S, Muster B, Bereiter-Hahn J, Jendrach M (2014) Autophagy proteins LC3B, ATG5 and ATG12 participate in quality control after mitochondrial damage and influence lifespan. Autophagy 8:47–62. doi:10.4161/auto.8.1.18174 PubMed—NCBI
Mair W, Morantte I, Rodrigues APC et al (2011) Lifespan extension induced by AMPK and calcineurin is mediated by CRTC-1 and CREB. Nature 470:404–408. doi:10.1038/nature09706
Mancuso R, Navarro X (2015) Amyotrophic lateral sclerosis: current perspectives from basic research to the clinic. Prog Neurobiol 133:1–26. doi:10.1016/j.pneurobio.2015.07.004
Marino G, Salvador-Montoliu N, Fueyo A et al (2007) Tissue-specific autophagy alterations and increased tumorigenesis in mice deficient in Atg4C/Autophagin-3. J Biol Chem 282:18573–18583. doi:10.1074/jbc.m701194200
Martinez J, Malireddi RKS, Lu Q et al (2015) Molecular characterization of LC3-associated phagocytosis reveals distinct roles for Rubicon, NOX2 and autophagy proteins. Nat Cell Biol 17:893–906. doi:10.1038/ncb3192
Maruyama H, Morino H, Ito H et al (2010) Mutations of optineurin in amyotrophic lateral sclerosis. Nature 465:223–226. doi:10.1038/nature08971
Masiero E, Agatea L, Mammucari C et al (2009) Autophagy is required to maintain muscle mass. Cell Metab 10:507–515. doi:10.1016/j.cmet.2009.10.008
Mathew R, Karp CM, Beaudoin B et al (2009) Autophagy suppresses tumorigenesis through elimination of p62. Cell 137:1062–1075. doi:10.1016/j.cell.2009.03.048
Mathew R, Kongara S, Beaudoin B et al (2007) Autophagy suppresses tumor progression by limiting chromosomal instability. Genes Dev 21:1367–1381. doi:10.1101/gad.1545107
Matsuda N, Sato S, Shiba K et al (2010) PINK1 stabilized by mitochondrial depolarization recruits Parkin to damaged mitochondria and activates latent Parkin for mitophagy. J Cell Biol 189:211–221. doi:10.1083/jcb.200910140
Matsui M, Yamamoto A, Kuma A et al (2006) Organelle degradation during the lens and erythroid differentiation is independent of autophagy. Biochem Biophys Res Commun 339:485–489. doi:10.1016/j.bbrc.2005.11.044
Medina DL, Fraldi A, Bouche V et al (2011) Transcriptional activation of lysosomal exocytosis promotes cellular clearance. Dev Cell 21:421–430. doi:10.1016/j.devcel.2011.07.016
Melendez A (2003) Autophagy genes are essential for dauer development and life-span extension in C. elegans. Science 301:1387–1391. doi:10.1126/science.1087782
Menzies FM, Fleming A, Rubinsztein DC (2015) Compromised autophagy and neurodegenerative diseases. Nat Rev Neurosci 16:345–357. doi:10.1038/nrn3961
Menzies FM, Garcia-Arencibia M, Imarisio S et al (2014) Calpain inhibition mediates autophagy-dependent protection against polyglutamine toxicity. Cell Death Differ 22:433–444. doi:10.1038/cdd.2014.151
Menzies FM, Huebener J, Renna M et al (2010) Autophagy induction reduces mutant ataxin-3 levels and toxicity in a mouse model of spinocerebellar ataxia type 3. Brain 133:93–104. doi:10.1093/brain/awp292
Merz EA, Brinster RL, Brunner S, Chen HY (1981) Protein degradation during preimplantation development of the mouse. J Reprod Fertil 61:415–418
Metzger S, Saukko M, Van Che H et al (2010) Age at onset in Huntington’s disease is modified by the autophagy pathway: implication of the V471A polymorphism in Atg7. Hum Genet 128:453–459. doi:10.1007/s00439-010-0873-9
Mizushima N (2004) In Vivo analysis of autophagy in response to nutrient starvation using transgenic mice expressing a fluorescent autophagosome marker. Mol Biol Cell 15:1101–1111. doi:10.1091/mbc.E03-09-0704
Mizushima N, Komatsu M (2011) Autophagy: renovation of cells and tissues. Cell 147:728–741. doi:10.1016/j.cell.2011.10.026
Mizushima N, Levine B (2010) Autophagy in mammalian development and differentiation. Nat Cell Biol 12:823–830. doi:10.1038/ncb0910-823
Morimoto N, Nagai M, Ohta Y et al (2007) Increased autophagy in transgenic mice with a G93A mutant SOD1 gene. Brain Res 1167:112–117. doi:10.1016/j.brainres.2007.06.045
Mortensen M, Ferguson DJP, Edelmann M et al (2010) Loss of autophagy in erythroid cells leads to defective removal of mitochondria and severe anemia in vivo. Proc Natl Acad Sci USA 107:832–837. doi:10.1073/pnas.0913170107
Nagata E, Sawa A, Ross CA, Snyder SH (2004) Autophagosome-like vacuole formation in Huntington’s disease lymphoblasts. NeuroReport 15:1325–1328
Nakagawa I (2004) Autophagy defends cells against invading group a streptococcus. Science 306:1037–1040. doi:10.1126/science.1103966
Nakahira K, Haspel JA, Rathinam VAK et al (2010) Autophagy proteins regulate innate immune responses by inhibiting the release of mitochondrial DNA mediated by the NALP3 inflammasome. Nat Immunol 12:222–230. doi:10.1038/ni.1980 PubMed—NCBI
Nakai A, Yamaguchi O, Takeda T et al (2007) The role of autophagy in cardiomyocytes in the basal state and in response to hemodynamic stress. Nat Med 13:619–624. doi:10.1038/nm1574
Narendra D, Tanaka A, Suen D-F, Youle RJ (2008) Parkin is recruited selectively to impaired mitochondria and promotes their autophagy. J Cell Biol 183:795–803. doi:10.1083/jcb.200809125
Narendra DP, Jin SM, Tanaka A et al (2010) PINK1 Is selectively stabilized on impaired mitochondria to activate Parkin. PLoS Biol 8:e1000298. doi:10.1371/journal.pbio.1000298
Nedjic J, Aichinger M, Emmerich J et al (2008) Autophagy in thymic epithelium shapes the T-cell repertoire and is essential for tolerance. Nature 455:396–400 PubMed—NCBI
Nishida Y, Arakawa S, Fujitani K et al (2009) Discovery of Atg5/Atg7-independent alternative macroautophagy. Nature 461:654–658. doi:10.1038/nature08455
Niu H, Xiong Q, Yamamoto A et al (2012) Autophagosomes induced by a bacterial Beclin 1 binding protein facilitate obligatory intracellular infection. Proc Natl Acad Sci USA 109:20800–20807. doi:10.1073/pnas.1218674109
Nixon RA, Wegiel J, Kumar A et al (2005) Extensive involvement of autophagy in Alzheimer disease: an immuno-electron microscopy study. J Neuropathol Exp Neurol 64:113–122
Novak I, Kirkin V, McEwan DG et al (2010) Nix is a selective autophagy receptor for mitochondrial clearance. EMBO Rep 11:45–51. doi:10.1038/embor.2009.256
Orvedahl A, MacPherson S, Sumpter R Jr et al (2010) Autophagy protects against Sindbis virus infection of the central nervous system. Cell Host Microbe 7:115–127. doi:10.1016/j.chom.2010.01.007
Otto GP, Wu MY, Kazgan N et al (2003) Macroautophagy is required for multicellular development of the social amoeba Dictyostelium discoideum. J Biol Chem 278:17636–17645. doi:10.1074/jbc.m212467200
Pengo N, Scolari M, Oliva L et al (2013) Plasma cells require autophagy for sustainable immunoglobulin production. Nat Immunol 14:298–305. doi:10.1038/ni.2524 PubMed—NCBI
Piccioli P, Rubartelli A (2013) The secretion of IL-1β and options for release. Semin Immunol 25:425–429. doi:10.1016/j.smim.2013.10.007 PubMed—NCBI
Pickford F, Masliah E, Britschgi M et al (2008) The autophagy-related protein Beclin 1 shows reduced expression in early Alzheimer disease and regulates amyloid β accumulation in mice. J Clin Invest. doi:10.1172/JCI33585
Polito VA, Li H, Martini-Stoica H et al (2014) Selective clearance of aberrant tau proteins and rescue of neurotoxicity by transcription factor EB. EMBO Mol Med 6:1142–1160. doi:10.15252/emmm.201303671
Ponpuak M, Mandell MA, Kimura T et al (2015) Secretory autophagy. Curr Opin Cell Biol 35:106–116. doi:10.1016/j.ceb.2015.04.016
Pryer NK, Wuestehube LJ, Schekman R (1992) Vesicle-mediated protein sorting. Annu Rev Biochem 61:471–516. doi:10.1146/annurev.bi.61.070192.002351
Pua HH, Dzhagalov I, Chuck M et al (2007) A critical role for the autophagy gene Atg5 in T cell survival and proliferation. J Exp Med 204:25–31. doi:10.1084/jem.20061303
Pua HH, Guo J, Komatsu M, He Y-W (2009) Autophagy is essential for mitochondrial clearance in mature T lymphocytes. J Immunol (Baltimore, Md: 1950) 182:4046–4055. doi:10.4049/jimmunol.0801143
Puleston DJ, Zhang H, Powell TJ, et al (2014) Autophagy is a critical regulator of memory CD8+T cell formation. eLife 3:2516. doi:10.7554/eLife.03706
Pyo J-O, Yoo S-M, Ahn H-H et al (2013) Overexpression of Atg5 in mice activates autophagy and extends lifespan. Nat commun 4:2300. doi:10.1038/ncomms3300
Qin Z-H, Wang Y, Kegel KB et al (2003) Autophagy regulates the processing of amino terminal huntingtin fragments. Hum Mol Genet 12:3231–3244. doi:10.1093/hmg/ddg346
Qu X, Yu J, Bhagat G et al (2003) Promotion of tumorigenesis by heterozygous disruption of the Beclin 1 autophagy gene. J Clin Invest 112:1809–1820. doi:10.1172/JCI20039
Qu X, Zou Z, Sun Q et al (2007) Autophagy gene-dependent clearance of apoptotic cells during embryonic development. Cell 128:931–946. doi:10.1016/j.cell.2006.12.044
Raben N, Hill V, Shea L et al (2008) Suppression of autophagy in skeletal muscle uncovers the accumulation of ubiquitinated proteins and their potential role in muscle damage in Pompe disease. Hum Mol Genet 17:3897–3908. doi:10.1093/hmg/ddn292
Rabinowitz JD, White E (2010) Autophagy and metabolism. Science 330:1344–1348. doi:10.1126/science.1193497 (New York, NY)
Randow F, Youle RJ (2014) Self and nonself: how autophagy targets mitochondria and bacteria. Cell Host Microbe 15:403–411. doi:10.1016/j.chom.2014.03.012
Rao S, Tortola L, Perlot T et al (2014) A dual role for autophagy in a murine model of lung cancer. Nat commun 5:3056. doi:10.1038/ncomms4056
Ravikumar B (2002) Aggregate-prone proteins with polyglutamine and polyalanine expansions are degraded by autophagy. Hum Mol Genet 11:1107–1117. doi:10.1093/hmg/11.9.1107
Ravikumar B, Vacher C, Berger Z et al (2004) Inhibition of mTOR induces autophagy and reduces toxicity of polyglutamine expansions in fly and mouse models of Huntington disease. Nat Genet 36:585–595. doi:10.1038/ng1362
Razani B, Feng C, Coleman T et al (2012) Autophagy links inflammasomes to atherosclerotic progression. Cell Metab 15:534–544. doi:10.1016/j.cmet.2012.02.011
Rioux JD, Xavier RJ, Taylor KD et al (2007) Genome-wide association study identifies five novel susceptibility loci for Crohn’s disease and implicates a role for autophagy in disease pathogenesis. Nat Genet 39:596–604. doi:10.1038/ng2032
Rodríguez-Muela N, Germain F, Marino G et al (2011) Autophagy promotes survival of retinal ganglion cells after optic nerve axotomy in mice. Cell Death Differ 19:162–169. doi:10.1038/cdd.2011.88
Rodríguez-Navarro JA, Rodríguez L, Casarejos MJ et al (2010) Trehalose ameliorates dopaminergic and tau pathology in parkin deleted/tau overexpressing mice through autophagy activation. Neurobiol Dis 39:423–438. doi:10.1016/j.nbd.2010.05.014
Rogov V, Dötsch V, Johansen T, Kirkin V (2014) Interactions between autophagy receptors and ubiquitin-like proteins form the molecular basis for selective autophagy. Mol Cell 53:167–178. doi:10.1016/j.molcel.2013.12.014
Rose C, Menzies FM, Renna M et al (2010) Rilmenidine attenuates toxicity of polyglutamine expansions in a mouse model of Huntington’s disease. Hum Mol Genet 19:2144–2153. doi:10.1093/hmg/ddq093
Rosenfeldt MT, O’Prey J, Morton JP et al (2013) p53 status determines the role of autophagy in pancreatic tumour development. Nature 504:296–300. doi:10.1038/nature12865 PubMed—NCBI
Rubinsztein DC, Codogno P, Levine B (2012) Autophagy modulation as a potential therapeutic target for diverse diseases. Nat Rev Drug Discov 11:709–730. doi:10.1038/nrd3802
Rudnicki DD, Pletnikova O, Vonsattel J-PG et al (2008) A comparison of Huntington disease and Huntington disease-like 2 neuropathology. J Neuropathol Exp Neurol 67:366–374. doi:10.1097/NEN.0b013e31816b4aee PubMed—NCBI
Rui Y-N, Xu Z, Patel B et al (2015) Huntingtin functions as a scaffold for selective macroautophagy. Nat Cell Biol 17:262–275. doi:10.1038/ncb3101
Russell SE, Hickey GI, Lowry WS et al (1990) Allele loss from chromosome 17 in ovarian cancer. Oncogene 5:1581–1583
Ryoo HD, Baehrecke EH (2010) Distinct death mechanisms in Drosophila development. Curr Opin Cell Biol 22:889–895. doi:10.1016/j.ceb.2010.08.022
Saito H, Inazawa J, Saito S et al (1993) Detailed deletion mapping of chromosome 17q in ovarian and breast cancers: 2-cM region on 17q21.3 often and commonly deleted in tumors. Cancer Res 53:3382–3385
Saitoh T, Fujita N, Hayashi T et al (2009) Atg9a controls dsDNA-driven dynamic translocation of STING and the innate immune response. Proc Natl Acad Sci USA 106:20842–20846. doi:10.1073/pnas.0911267106
Saitoh T, Fujita N, Jang MH et al (2008) Loss of the autophagy protein Atg16L1 enhances endotoxin-induced IL-1|[bgr]| production. Nature 456:264–268. doi:10.1038/nature07383
Sandoval H, Thiagarajan P, Dasgupta SK et al (2008) Essential role for Nix in autophagic maturation of erythroid cells. Nature 454:232–235. doi:10.1038/nature07006
Sanjuan MA, Dillon CP, Tait SWG et al (2007) Toll-like receptor signalling in macrophages links the autophagy pathway to phagocytosis. Nature 450:1253–1257. doi:10.1038/nature06421
Sarkar S, Floto RA, Berger Z et al (2005) Lithium induces autophagy by inhibiting inositol monophosphatase. J Cell Biol 170:1101–1111. doi:10.1083/jcb.200504035
Sarraf SA, Raman M, Guarani-Pereira V et al (2013) Landscape of the PARKIN-dependent ubiquitylome in response to mitochondrial depolarization. Nature 496:372–376. doi:10.1038/nature12043 PubMed—NCBI
Sasaki S (2011) Autophagy in spinal cord motor neurons in sporadic amyotrophic lateral sclerosis. J Neuropathol Exp Neurol 70:349–359. doi:10.1097/NEN.0b013e3182160690
Sato M, Sato K (2011) Degradation of paternal mitochondria by fertilization-triggered autophagy in C. elegans embryos. Science 334:1141–1144. doi:10.1126/science.1210333 PubMed—NCBI
Schaeffer V, Lavenir I, Ozcelik S et al (2012) Stimulation of autophagy reduces neurodegeneration in a mouse model of human tauopathy. Brain 135:2169–2177. doi:10.1093/brain/aws143
Schwarten M, Mohrlüder J, Ma P et al (2009) Nix directly binds to GABARAP: a possible crosstalk between apoptosis and autophagy. Autophagy 5:690–698
Schweers RL, Zhang J, Randall MS et al (2007) NIX is required for programmed mitochondrial clearance during reticulocyte maturation. Proc Natl Acad Sci USA 104:19500–19505. doi:10.1073/pnas.0708818104
Settembre C, Ballabio A (2014) Lysosome: regulator of lipid degradation pathways. Trends Cell Biol 24:743–750. doi:10.1016/j.tcb.2014.06.006
Sherrington R, Rogaev EI, Liang Y et al (1995) Cloning of a gene bearing missense mutations in early-onset familial Alzheimer’s disease. Nature 375:754–760. doi:10.1038/375754a0
Shibata M, Lu T, Furuya T et al (2006) Regulation of intracellular accumulation of mutant Huntingtin by Beclin 1. J Biol Chem 281:14474–14485. doi:10.1074/jbc.M600364200
Shibata M, Yoshimura K, Tamura H et al (2010) LC3, a microtubule-associated protein1A/B light chain3, is involved in cytoplasmic lipid droplet formation. Biochem Biophys Res Commun 393:274–279. doi:10.1016/j.bbrc.2010.01.121 PubMed—NCBI
Shibutani ST, Saitoh T, Nowag H et al (2015) Autophagy and autophagy-related proteins in the immune system. Nat Immunol 16:1014–1024 PubMed—NCBI
Shimada K, Motoi Y, Ishiguro K et al (2012) Long-term oral lithium treatment attenuates motor disturbance in tauopathy model mice: Implications of autophagy promotion. Neurobiol Dis 46:101–108. doi:10.1016/j.nbd.2011.12.050
Simonsen A, Brech A (2014) Promoting basal levels of autophagy in the nervous system enhances longevity and oxidant resistance in adult Drosophila. Autophagy 4:176–184. doi:10.4161/auto.5269
Singh R, Xiang Y, Wang Y et al (2009) Autophagy regulates adipose mass and differentiation in mice. J Clin Investig 119:3329–3339. doi:10.1172/JCI39228
Singleton AB, Farrer M, Johnson J et al (2003) Alpha-Synuclein locus triplication causes Parkinson’s disease. Science 302:841. doi:10.1126/science.1090278 (New York, NY)
Song S, Jang S, Park J et al (2013) Characterization of PINK1 (PTEN-induced putative kinase 1) mutations associated with Parkinson disease in mammalian cells and Drosophila. J Biol Chem 288:5660–5672. doi:10.1074/jbc.M112.430801
Sorbara MT, Girardin SE (2015) Emerging themes in bacterial autophagy. Curr Opin Microbiol 23:163–170. doi:10.1016/j.mib.2014.11.020
Sou YS, Waguri S, Iwata JI et al (2008) The Atg8 conjugation system is indispensable for proper development of autophagic isolation membranes in mice. Mol Biol Cell 19:4762–4775. doi:10.1091/mbc.E08-03-0309
Spilman P, Podlutskaya N, Hart MJ et al (2010) Inhibition of mTOR by rapamycin abolishes cognitive deficits and reduces amyloid-β levels in a mouse model of alzheimer’s disease. PLoS ONE 5:e9979. doi:10.1371/journal.pone.0009979
Sriram SR, Li X, Ko HS et al (2005) Familial-associated mutations differentially disrupt the solubility, localization, binding and ubiquitination properties of Parkin. Hum Mol Genet 14:2571–2586. doi:10.1093/hmg/ddi292
Stappenbeck TS, Rioux JD, Mizoguchi A et al (2011) Crohn disease: a current perspective on genetics, autophagy and immunity. Autophagy 7:355–374. doi:10.4161/auto.7.4.13074
Stefanis L, Larsen KE, Rideout HJ et al (2001) Expression of A53T mutant but not wild-type α-Synuclein in PC12 cells induces alterations of the ubiquitin-dependent degradation system, loss of dopamine release, and autophagic cell death. J Neurosci 21:9549–9560. doi:10.1016/S0304-3940(00)01049-1
Stephenson LM, Miller BC, Ng A et al (2009) Identification of Atg5-dependent transcriptional changes and increases in mitochondrial mass in Atg5-deficient T lymphocytes. Autophagy 5:625–635. doi:10.4161/auto.5.5.8133
Stitzel ML, Seydoux G (2007) Regulation of the oocyte-to-zygote transition. Science 316:407–408. doi:10.1126/science.1138236 (New York, NY)
Sun B, Karin M (2013) Inflammation and liver tumorigenesis. Front Med 7:242–254. doi:10.1007/s11684-013-0256-4
Takamura A, Komatsu M, Hara T et al (2011) Autophagy-deficient mice develop multiple liver tumors. Genes Dev 25:795–800. doi:10.1101/gad.2016211 PubMed—NCBI
Tal MC, Sasai M, Lee HK et al (2009) Absence of autophagy results in reactive oxygen species-dependent amplification of RLR signaling. Proc Natl Acad Sci USA 106:2770–2775. doi:10.1073/pnas.0807694106
Taneike M, Yamaguchi O, Nakai A et al (2014) Inhibition of autophagy in the heart induces age-related cardiomyopathy. Autophagy 6:600–606. doi:10.4161/auto.6.5.11947
Tangir J, Muto MG, Berkowitz RS et al (1996) A 400 kb novel deletion unit centromeric to the BRCA1 gene in sporadic epithelial ovarian cancer. Oncogene 12:735–740
Tattoli I, Philpott DJ, Girardin SE (2012a) The bacterial and cellular determinants controlling the recruitment of mTOR to the Salmonella-containing vacuole. Biol Open 1:1215–1225. doi:10.1242/bio.20122840
Tattoli I, Sorbara MT, Vuckovic D et al (2012b) Amino acid starvation induced by invasive bacterial pathogens triggers an innate host defense program. Cell Host Microbe 11:563–575. doi:10.1016/j.chom.2012.04.012
Tattoli I, Sorbara MT, Yang C et al (2013) Listeria phospholipases subvert host autophagic defenses by stalling pre-autophagosomal structures. EMBO J 32:3066–3078. doi:10.1038/emboj.2013.234
Teyssou E, Takeda T, Lebon V et al (2013) Mutations in SQSTM1 encoding p62 in amyotrophic lateral sclerosis: genetics and neuropathology. Acta Neuropathol 125:511–522. doi:10.1007/s00401-013-1090-0
Tian Y, Bustos V, Flajolet M, Greengard P (2011) A small-molecule enhancer of autophagy decreases levels of Aβ and APP-CTF via Atg5-dependent autophagy pathway. FASEB J 25:1934–1942. doi:10.1096/fj.10-175158
Tooze J, Davies HG (1965) Cytolysomes in amphibian erythrocytes. J Cell Biol 24:146–150
Tóth ML, Sigmond T, Borsos E et al (2008) Longevity pathways converge on autophagy genes to regulate life span in Caenorhabditis elegans. Autophagy 4:330–338
Tsukada M, Ohsumi Y (1993) Isolation and characterization of autophagy-defective mutants of Saccharomyces cerevisiae. FEBS Lett 333:169–174. doi:10.1016/0014-5793(93)80398-E
Tsukamoto S, Kuma A, Murakami M et al (2008) Autophagy is essential for preimplantation development of mouse embryos. Science 321:117–120. doi:10.1126/science.1154822
Valente EM, Abou-Sleiman PM, Caputo V et al (2004) Hereditary early-onset Parkinson’s disease caused by mutations in PINK1. Science 304:1158–1160. doi:10.1126/science.1096284 (New York, NY)
Valente EM, Bentivoglio AR, Dixon PH et al (2001) Localization of a novel locus for autosomal recessive early-onset parkinsonism, PARK6, on human chromosome 1p35-p36. Am J Hum Genet 68:895–900
Valente EM, Brancati F, Caputo V et al (2002) PARK6 is a common cause of familial parkinsonism. Neurol Sci 23:s117–s118. doi:10.1007/s100720200097
Vijg J, Campisi J (2008) Puzzles, promises and a cure for ageing. Nature 454:1065–1071. doi:10.1038/nature07216
Vingtdeux V, Chandakkar P, Zhao H et al (2011) Novel synthetic small-molecule activators of AMPK as enhancers of autophagy and amyloid- peptide degradation. FASEB J 25:219–231. doi:10.1096/fj.10-167361
Vives-Bauza C, Zhou C, Huang Y et al (2010) PINK1-dependent recruitment of Parkin to mitochondria in mitophagy. Proc Natl Acad Sci USA 107:378–383. doi:10.1073/pnas.0911187107
Vogelstein B, Papadopoulos N, Velculescu VE et al (2013) Cancer genome landscapes. Science 339:1546–1558. doi:10.1126/science.1235122 PubMed—NCBI
Wei H, Wei S, Gan B et al (2011) Suppression of autophagy by FIP200 deletion inhibits mammary tumorigenesis. Genes Dev 25:1510–1527. doi:10.1101/gad.2051011
Wen H, Gris D, Lei Y et al (2011) Fatty acid–induced NLRP3-ASC inflammasome activation interferes with insulin signaling. Nat Immunol 12:408–415. doi:10.1038/ni.2022
White E (2012) Deconvoluting the context-dependent role for autophagy in cancer. Nat Rev Cancer 12:401–410. doi:10.1038/nrc3262
White E (2015) The role for autophagy in cancer. J Clin Invest 125:42–46. doi:10.1172/JCI73941 PubMed—NCBI
Wilkinson S, Ryan KM (2010) Autophagy: an adaptable modifier of tumourigenesis. Curr Opin Genet Dev 20:57–64. doi:10.1016/j.gde.2009.12.004 PubMed—NCBI
Winslow AR, Chen C-W, Corrochano S et al (2010) α-Synuclein impairs macroautophagy: implications for Parkinson’s disease. J Cell Biol 190:1023–1037. doi:10.1083/jcb.201003122
Wohlgemuth SE, Seo AY, Marzetti E, Lees HA, Leeuwenburgh C (2010) Skeletal muscle autophagy and apoptosis during aging: effects of calorie restriction and life-long exercise. Exp Gerontol 45:138–148. doi:10.1016/j.exger.2009.11.002
Wong E, Cuervo AM (2010) Autophagy gone awry in neurodegenerative diseases. Nat Neurosci 13:805–811. doi:10.1038/nn.2575
Wong YC, Holzbaur ELF (2015) Autophagosome dynamics in neurodegeneration at a glance. J Cell Sci 128:1259–1267. doi:10.1242/jcs.161216
Xu X, Araki K, Li S et al (2014) Autophagy is essential for effector CD8(+) T cell survival and memory formation. Nat Immunol 15:1152–1161. doi:10.1038/ni.3025 PubMed—NCBI
Yang A, Rajeshkumar NV, Wang X et al (2014) Autophagy is critical for pancreatic tumor growth and progression in tumors with p53 alterations. Cancer Discov 4:905–913. doi:10.1158/2159-8290.CD-14-0362
Yang J-Y, Yang WY (2013) Bit-by-bit autophagic removal of parkin-labelled mitochondria. Nat commun. doi:10.1038/ncomms3428
Yang S, Wang X, Contino G et al (2011) Pancreatic cancers require autophagy for tumor growth. Genes Dev 25:717–729. doi:10.1101/gad.2016111 PubMed—NCBI
Yordy B, Tal MC, Hayashi K et al (2013) Autophagy and selective deployment of Atg proteins in antiviral defense. Int Immunol 25:1–10. doi:10.1093/intimm/dxs101
Yue Z, Jin S, Yang C et al (2003) Beclin 1, an autophagy gene essential for early embryonic development, is a haploinsufficient tumor suppressor. Proc Nat Acad Sci USA 100:15077–15082. doi:10.1073/pnas.2436255100
Zhang J, Randall MS, Loyd MR et al (2009a) Mitochondrial clearance is regulated by Atg7-dependent and -independent mechanisms during reticulocyte maturation. Blood 114:157–164. doi:10.1182/blood-2008-04-151639
Zhang M, Kenny SJ, Ge L, et al (2015) Translocation of interleukin-1β into a vesicle intermediate in autophagy-mediated secretion. eLife 4:1463. doi:10.7554/eLife.11205
Zhang M, Schekman R (2013) Cell biology. Unconventional secretion, unconventional solutions. Science 340:559–561 PubMed—NCBI
Zhang X, Chen S, Song L et al (2014) MTOR-independent, autophagic enhancer trehalose prolongs motor neuron survival and ameliorates the autophagic flux defect in a mouse model of amyotrophic lateral sclerosis. Autophagy 10:588–602. doi:10.4161/auto.27710
Zhang Y, Goldman S, Baerga R et al (2009b) Adipose-specific deletion of autophagy-related gene 7 (atg7) in mice reveals a role in adipogenesis. Proc Nat Acad Sci USA 106:19860–19865. doi:10.1073/pnas.0906048106
Zheng S, Clabough EBD, Sarkar S et al (2010) Deletion of the huntingtin polyglutamine stretch enhances neuronal autophagy and longevity in mice. PLoS Genet 6:e1000838. doi:10.1371/journal.pgen.1000838
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Karanasios, E., Ktistakis, N.T. (2016). Physiological Role of Autophagy and Implications in Disease. In: Autophagy at the Cell, Tissue and Organismal Level. SpringerBriefs in Cell Biology. Springer, Cham. https://doi.org/10.1007/978-3-319-33145-4_5
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