Department of Pediatrics, West China Second Hospital, Sichuan University/Key Laboratory of Birth Defects and Related Diseases of Women and Children, Ministry of Education/Key Laboratory of Development and Related Diseases of Women and Children, Chengdu 610041, China
Abstract：Mitophagy is a process during which the cell selectively removes the mitochondria via the mechanism of autophagy. It is crucial to the functional completeness of the whole mitochondrial network and determines cell survival and death. On the one hand, the damaged mitochondria releases pro-apoptotic factors which induce cell apoptosis; on the other hand, the damaged mitochondria eliminates itself via autophagy, which helps to maintain cell viability. Mitophagy is of vital importance for the development and function of the nervous system. Neural cells rely on autophagy to control protein quality and eliminate the damaged mitochondria, and under normal circumstances, mitophagy can protect the neural cells. Mutations in genes related to mitophagy may cause the development and progression of neurodegenerative diseases. An understanding of the role of mitophagy in nervous system diseases may provide new theoretical bases for clinical treatment. This article reviews the research advances in the relationship between mitophagy and different types of nervous system diseases.
Mitchell T, Chacko B, Ballinger SW, et al. Convergent mechanisms for dysregulation of mitochondrial quality control in metabolic disease:implications for mitochondrial therapeutics[J]. Biochem Soc Trans, 2013, 41(1):127-133.
[2]
Dodson M, Darley-Usmar V, Zhang J. Cellular metabolic and autophagic pathways:traffic control by redox signaling[J]. Free Radic Biol Med, 2013, 63(10):207-221.
[3]
Zhang J. Autophagy and mitophagy in cellular damage control[J]. Redox Biology, 2013, 1(1):19-23.
[4]
Lemasters JJ. Selective mitochondrial autophagy, or mitophagy, as a targeted defense against oxidative stress, mitochondrial dysfunction, and aging[J]. Rejuvenation Res, 2005, 8(1):3-5.
[5]
Lemasters JJ. Variants of mitochondrial autophagy:Types 1 and 2 mitophagy and micromitophagy (Type 3)[J]. Redox Biol, 2014, 2(1):749-754.
[6]
Huang H, Yang L, Zhang P, et al. Real-time tracking mitochondrial dynamic remodeling with two-photon phosphorescent iridium (III) complexes[J]. Biomaterials, 2016, 83:321-331.
[7]
Twig G, Elorza A, Molina AJ, et al. Fission and selective fusion govern mitochondrial segregation and elimination by autophagy[J]. Embo J, 2008, 27(2):433-446.
[8]
Ji WK, Hatch AL, Merrill RA, et al. Actin filaments target the oligomeric maturation of the dynamin GTPase Drp1 to mitochondrial fission sites[J]. Elife, 2015, 4:e11553.
[9]
Fukumitsu K, Hatsukano T, Yoshimuraa, et al. Mitochondrial fission protein Drp1 regulates mitochondrial transport and dendritic arborization in cferebellar Purkinje cells[J]. Mol Cell Neurosci, 2016, 71:56-65.
[10]
Lee JY, Kapur M, Li M, et al. MFN1 deacetylation activates adaptive mitochondrial fusion and protects metabolically challenged mitochondria[J]. J Cell Sci, 2014, 127(Pt 22):4954-4963.
Macvicar TD, Lane JD. Impaired OMA1-dependent cleavage of OPA1 and reduced DRP1 fission activity combine to prevent mitophagy in cells that are dependent on oxidative phosphorylation[J]. J Cell Sci, 2014, 127(10):2313-2325.
[13]
Liu L, Sakakibara K, Chen Q, et al. Receptor-mediated mitophagy in yeast and mammalian systems[J]. Cell Res, 2014, 24(7):787-795.
[14]
Nardin A, Schrepfer E, Ziviani E. Counteracting PINK/Parkin deficiency in the activation of mitophagy:A potential therapeutic intervention for Parkinson's disease[J]. Curr Neuropharmacol, 2016, 14(3):250-259.
[15]
Heo JM, Ordureau A, Paulo JA, et al. The PINK1-PARKIN mitochondrial ubiquitylation pathway drives a program of OPTN/NDP52 recruitment and TBK1 activation to promote mitophagy[J]. Mol Cell, 2015, 60(1):7-20.
[16]
Ghazaleh A, Julia S, Matthew JL, et al. Mitophagy of damaged mitochondria occurs locally in distal neuronal axons and requires PINK1 and Parkin[J]. J Cell Biol, 2014, 206(5):655-670.
[17]
Ziviani E, Tao RN, Whitworth AJ. Drosophila parkin requires PINK1 for mitochondrial translocation and ubiquitinates mitofusin[J]. Proc Natl Acad Sci U S A, 2010, 107(11):5018-5023.
[18]
Wang H, Song P, Du L, et al. Parkin ubiquitinates Drp1 for proteasome-dependent degradation:implication of dysregulated mitochondrial dynamics in Parkinson disease[J]. J Biol Chem, 2011, 286(13):11649-11658.
[19]
Lazarou M, Sliter Da, Kane La, et al. The ubiquitin kinase PINK1 recruits autophagy receptors to induce mitophagy[J]. Nature, 2015, 524(7565):309-314.
[20]
Gao J, Qin S, Jiang C. Parkin-induced ubiquitination of Mff promotes its association with P62/SQSTM1 during mitochondrial depolarization[J]. Acta Biochim Biophys Sin(Shanghai), 2015, 47(7):522-529.
[21]
Ney PA. Mitochondrial autophagy:Origins, significance, and role of BNIP3 and NIX[J]. Biochim Biophys Acta, 2015, 1853(10 Pt B):2775-2783.
[22]
Hanna RA, Quinsay MN, Orogo AM, et al. Microtubule-associated protein 1 light chain 3(LC3) interacts with Bnip3 protein to selectively remove endoplasmic reticulum and mitochondria via autophagy[J]. J Biol Chem, 2012, 287(23):19094-19104.
[23]
Sandoval H, Thiagarajan P, Dasgupta SK, et al. Essential role for Nix in autophagic maturation of erythroid cells[J]. Nature, 2008, 454(7201):232-235.
[24]
Wu LY, Ma ZM, Fan XL, et al. The anti-necrosis role of hypoxic preconditioning after acute anoxia is mediated by aldose reductase and sorbitol pathway in PC12 cells[J]. Cell Stress Chaperones, 2010, 15(4):387-394.
[25]
Chen G, Han Z, Feng D, et al. A regulatory signaling loop comprising the PGAM5 phosphatase and CK2 controls receptor-mediated mitophagy[J]. Mol Cell, 2014, 54(3):362-377.
[26]
Wu H, Xue D, Chen G, et al. The BCL2L1 and PGAM5 axis defines hypoxia-induced receptor-mediated mitophagy[J]. Autophagy, 2014, 10(10):1712-1725.
[27]
Lu W, Sun J, Yoon JS, et al. Mitochondrial protein PGAM5 regulates mitophagic protection against cell necroptosis[J]. PLoS One, 2016, 11(1):e0147792.
[28]
Van Humbeeck C, Cornelissen T, Hofkens H, et al. Parkin interacts with Ambra1 to induce mitophagy[J]. J Neurosci, 2011, 31(28):10249-10261.
[29]
Strappazzon F. AMBRA1 is able to induce mitophagy via LC3 binding, regardless of PARKIN and p62/SQSTM1[J]. Cell Death Differ, 2015, 22(3):419-432.
[30]
Chu CT, Ji J, Dagda RK, et al. Cardiolipin externalization to the outer mitochondrial membrane acts as an elimination signal for mitophagy in neuronal cells[J]. Nat Cell Biol, 2013, 15(10):1197-1205.
[31]
Awasthi M, Singh S, Pandey VP, et al. Alzheimer's disease:An overview of amyloid beta dependent pathogenesis and its therapeutic implications along with in silico approaches emphasizing the role of natural products[J]. J Neurol Sci, 2016, 361:256-271.
[32]
Reddy PH, Manczak M, Mao P, et al. Amyloid-beta and mitochondria in aging and Alzheimer's disease:implications for synaptic damage and cognitive decline[J]. J Alzheimers Dis, 2010, 20(Suppl 2):S499-S512.
[33]
Carvalho C, Santos MS, Oliveira CR, et al. Alzheimer's disease and type 2 diabetes-related alterations in brain mitochondria, autophagy and synaptic markers[J]. Biochim Biophys Acta, 2015, 1852(8):1665-1675.
[34]
Du H, Guo L, Yan S, et al. Early deficits in synaptic mitochondria in an Alzheimer's disease mouse model[J]. Proc Natl Acad Sci U S A, 2010, 107(43):18670-18675.
[35]
Khandelwal PJ, Herman AM, Hoe HS, et al. Parkin mediates beclin-dependent autophagic clearance of defective mitochondria and ubiquitinated Abeta in AD models[J]. Hum Mol Genet, 2011, 20(11):2091-2102.
[36]
Wang X, Wang W, Li L, et al. Oxidative stress and mitochondrial dysfunction in Alzheimer's disease[J]. Biochim Biophys Acta, 2014, 1842(8):1240-1247.
[37]
Deng H, Dodsonmw H, Huang H, et al. The Parkinsons disease genes Pink1 and Parkin promote mitochondrial fisson and inhibit fusion in drosophia[J]. Proc Natl Acad Sci U S A, 2008, 105(38):14503-14508.
[38]
Trinh J, Farrer M. Advances in the genetics of Parkinson disease[J]. Nat Rev Neurol, 2013, 9(8):445-454.
[39]
Geisler S, Holmström KM, Skujat D, et al. PINK1/Parkin-mediated mitophagy is dependent on VDAC1 and p62/SQSTM1[J]. Nat Cell Biol, 2010, 12(2):119-131.
[40]
Dagda RK, Zhu J, Chu CT. Mitochondrial kinases in Parkinson's disease:converging insights from neurotoxin and genetic models[J]. Mitochondrion, 2009, 9(5):289-298.
[41]
Sampaio-Marques B, Felgueiras C, Silva A, et al. SNCA (α-synuclein)-induced toxicity in yeast cells is dependent on sirtuin 2(Sir2)-mediated mitophagy[J]. Autophagy, 2012, 8(10):1494-1509.
[42]
Sanders LH, Mccoy J, Hu X, et al. Mitochondrial DNA damage:molecular marker of vulnerable nigral neurons in Parkinson's disease[J]. Neurobiol Dis, 2014, 70:214-223.
[43]
Pandey M, Varghese M, Sindhu KM, et al. Mitochondrial NAD+-linked State 3 respiration and complex-I activity are compromised in the cerebral cortex of 3-nitropropionic acid-induced rat model of Huntington's disease[J]. J Neurochem, 2008, 104(2):420-434.
[44]
Shirendeb U, Reddy AP, Manczak M, et al. Abnormal mitochondrial dynamics, mitochondrial loss and mutant huntingtin oligomers in Huntington's disease:implications for selective neuronal damage[J]. Hum Mol Genet, 2011, 20(7):1438-1455.
[45]
Kim J, Moody JP, Edgerly CK, et al. Mitochondrial loss, dysfunction and altered dynamics in Huntington's disease[J]. Hum Mol Genet, 2010, 19(20):3919-3935.
[46]
Pedrini S, Sau D, Guareschi S, et al. ALS-linked mutant SOD1 damages mitochondria by promoting conformational changes in Bcl-2[J]. Hum Mol Genet, 2010, 19(15):2974-2986.
[47]
Wong YC, Holzbaur EL. Optineurin is an autophagy receptor for damaged mitochondria in parkin-mediated mitophagy that is disrupted by an ALS-linked mutation.[J]. Proc Natl Acad Sci U S A, 2014, 111(42):E4439-E4448.
[48]
Lin MY, Sheng ZH. Regulation of mitochondrial transport in neurons[J]. Exp Cell Res, 2015, 334(1):35-44.
[49]
Shutt TE, Mcbride HM. Staying cool in difficult times:mitochondrial dynamics, quality control and the stress response[J]. Biochim Biophys Acta, 2013, 1833(2):417-424.
[50]
Shi R, Zhu S, Li V, et al. BNIP3 Interacting with LC3 triggers excessive mitophagy in delayed neuronal death in stroke[J]. CNS Neurosci Ther, 2014, 20(12):1045-1055.
[51]
Cavallucci V, Bisicchia E, Cencioni MT, et al. Acute focal brain damage alters mitochondrial dynamics and autophagy in axotomized neurons[J]. Cell Death Dis, 2014, 5:e1545.
[52]
Giorgi FS, Biagioni F, Lenzi P, et al. The role of autophagy in epileptogenesis and in epilepsy-induced neuronal alterations[J]. J Neural Transm (Vienna), 2015, 122(6):849-862.
[53]
邱小雪. 癫癎持续状态大鼠海马线粒体分裂、融合变化的研究[D]. 济南:山东大学, 2013.
[54]
Frye RE. Metabolic and mitochondrial disorders associated with epilepsy in children with autism spectrum disorder[J]. Epilepsy Behav, 2015, 47:147-157.
