Misconnecting the dots: altered mitochondrial protein-protein interactions and their role in neurodegenerative disorders

References

• Lin MT, Beal MF. Mitochondrial dysfunction and oxidative stress in neurodegenerative diseases. Nature. 2006;443(7113):787–795.
   PubMed Web of Science ®Google Scholar
• Nunnari J, Suomalainen A. Mitochondria: in sickness and in health. Cell. 2012;148(6):1145–1159.
   PubMed Web of Science ®Google Scholar
• Friedman JR, Nunnari J. Mitochondrial form and function. Nature. 2014;505(7483):335–343.
   PubMed Web of Science ®Google Scholar
• Prudent J, McBride HM. The mitochondria-endoplasmic reticulum contact sites: a signalling platform for cell death. Curr Opin Cell Biol. 2017;47:52–63.
   PubMed Web of Science ®Google Scholar
• Schrepfer E, Scorrano L. Mitofusins, from mitochondria to metabolism. Mol Cell. 2016;61(5):683–694.
   PubMed Web of Science ®Google Scholar
• Milenkovic D, Blaza JN, Larsson NG, et al. The enigma of the respiratory chain supercomplex. Cell Metab. 2017;25(4):765–776.
   PubMed Web of Science ®Google Scholar
• Kasahara A, Scorrano L. Mitochondria: from cell death executioners to regulators of cell differentiation. Trends Cell Biol. 2014;24(12):761–770.
   PubMed Web of Science ®Google Scholar
• Martin B, Mattson MP, Maudsley S. Caloric restriction and intermittent fasting: two potential diets for successful brain aging. Ageing Res Rev. 2006;5(3):332–353.
   PubMed Web of Science ®Google Scholar
• Guarente L. Mitochondria–a nexus for aging, calorie restriction, and sirtuins? Cellx. 2008;132(2):171–176.
   PubMed Web of Science ®Google Scholar
• Diogo CV, Yambire KF, Fernandez Mosquera L, et al. Mitochondrial adventures at the organelle society. Biochem Biophys Res Commun. 2018;500(1):87–93.
   PubMed Web of Science ®Google Scholar
• Pickles S, Vigie P, Youle RJ. Mitophagy and quality control mechanisms in mitochondrial maintenance. Curr Biol. 2018;28(4):R170–R185.
   PubMed Web of Science ®Google Scholar
• Manczak M, Reddy PH. Abnormal interaction between the mitochondrial fission protein Drp1 and hyperphosphorylated tau in Alzheimer’s disease neurons: implications for mitochondrial dysfunction and neuronal damage. Hum Mol Genet. 2012;21(11):2538–2547.
   PubMed Web of Science ®Google Scholar
• Manczak M, Calkins MJ, Reddy PH. Impaired mitochondrial dynamics and abnormal interaction of amyloid beta with mitochondrial protein Drp1 in neurons from patients with Alzheimer’s disease: implications for neuronal damage. Hum Mol Genet. 2011;20(13):2495–2509.
   PubMed Web of Science ®Google Scholar
• Seo JH, Rivadeneira DB, Caino MC, et al. The mitochondrial unfoldase-peptidase complex ClpXP controls bioenergetics stress and metastasis. PLoS Biol. 2016;14(7):e1002507.
   PubMed Web of Science ®Google Scholar
• Greene AW, Grenier K, Aguileta MA, et al. Mitochondrial processing peptidase regulates PINK1 processing, import and Parkin recruitment. EMBO Rep. 2012;13(4):378–385.
   PubMed Web of Science ®Google Scholar
• Strauss KA, Jinks RN, Puffenberger EG, et al. CODAS syndrome is associated with mutations of LONP1, encoding mitochondrial AAA+ Lon protease. Am J Hum Genet. 2015;96(1):121–135.
   PubMed Web of Science ®Google Scholar
• Royer-Bertrand B, Castillo-Taucher S, Moreno-Salinas R, et al. Mutations in the heat-shock protein A9 (HSPA9) gene cause the EVEN-PLUS syndrome of congenital malformations and skeletal dysplasia. Sci Rep. 2015;5:17154.
   PubMed Web of Science ®Google Scholar
• Malty RH, Jessulat M, Jin K, et al. Mitochondrial targets for pharmacological intervention in human disease. J Proteome Res. 2015;14(1):5–21.
   PubMed Web of Science ®Google Scholar
• Vlasblom J, Jin K, Kassir S, et al. Exploring mitochondrial system properties of neurodegenerative diseases through interactome mapping. J Proteomics. 2014;100:8–24.
   PubMed Web of Science ®Google Scholar
• Stefely JA, Kwiecien NW, Freiberger EC, et al. Mitochondrial protein functions elucidated by multi-omic mass spectrometry profiling. Nat Biotechnol. 2016;34(11):1191–1197.
   PubMed Web of Science ®Google Scholar
• Itzhak DN, Tyanova S, Cox J, et al. Global, quantitative and dynamic mapping of protein subcellular localization. Elife. 2016;5:e16950.
   Web of Science ®Google Scholar
• Morgenstern M, Stiller SB, Lubbert P, et al. Definition of a high-confidence mitochondrial proteome at quantitative scale. Cell Rep. 2017;19(13):2836–2852.
   PubMed Web of Science ®Google Scholar
• Scarpulla RC. Nucleus-encoded regulators of mitochondrial function: integration of respiratory chain expression, nutrient sensing and metabolic stress. Biochim Biophys Acta. 2012;1819(9–10):1088–1097.
   PubMed Web of Science ®Google Scholar
• Kang Y, Fielden LF, Stojanovski D. Mitochondrial protein transport in health and disease. Semin Cell Dev Biol. 2018;76:142–153.
   PubMed Web of Science ®Google Scholar
• Pfanner N, Warscheid B, Wiedemann N. Mitochondrial proteins: from biogenesis to functional networks. Nat Rev Mol Cell Biol. 2019;20(5):267–284.
   PubMed Web of Science ®Google Scholar
• Wasilewski M, Chojnacka K, Chacinska A. Protein trafficking at the crossroads to mitochondria. Biochim Biophys Acta Mol Cell Res. 2017;1864(1):125–137.
   PubMed Web of Science ®Google Scholar
• Rampelt H, Zerbes RM, van der Laan M, et al. Role of the mitochondrial contact site and cristae organizing system in membrane architecture and dynamics. Biochim Biophys Acta Mol Cell Res. 2017;1864(4):737–746.
   PubMed Web of Science ®Google Scholar
• Kozjak-Pavlovic V. The MICOS complex of human mitochondria. Cell Tissue Res. 2017;367(1):83–93.
   PubMed Web of Science ®Google Scholar
• Stoldt S, Wenzel D, Kehrein K, et al. Spatial orchestration of mitochondrial translation and OXPHOS complex assembly. Nat Cell Biol. 2018;20(5):528–534.
   PubMed Web of Science ®Google Scholar
• Anand R, Strecker V, Urbach J, et al. Mic13 is essential for formation of crista junctions in mammalian cells. PLoS One. 2016;11(8):e0160258.
   PubMed Web of Science ®Google Scholar
• Wurm CA, Neumann D, Lauterbach MA, et al. Nanoscale distribution of mitochondrial import receptor Tom20 is adjusted to cellular conditions and exhibits an inner-cellular gradient. Proc Natl Acad Sci U S A. 2011;108(33):13546–13551.
   PubMed Web of Science ®Google Scholar
• Cogliati S, Enriquez JA, Mitochondrial Cristae: SL. Where beauty meets functionality. Trends Biochem Sci. 2016;41(3):261–273.
   PubMed Web of Science ®Google Scholar
• Weinhaupl K, Lindau C, Hessel A, et al. Structural basis of membrane protein chaperoning through the mitochondrial intermembrane space. Cell. 2018;175(5):1365–1379 e1325.
   PubMed Web of Science ®Google Scholar
• Vogtle FN, Burkhart JM, Gonczarowska-Jorge H, et al. Landscape of submitochondrial protein distribution. Nat Commun. 2017;8(1):290.
   PubMedGoogle Scholar
• Pagliarini DJ, Calvo SE, Chang B, et al. A mitochondrial protein compendium elucidates complex I disease biology. Cell. 2008;134(1):112–123.
   PubMed Web of Science ®Google Scholar
• Jin K, Musso G, Vlasblom J, et al. Yeast mitochondrial protein-protein interactions reveal diverse complexes and disease-relevant functional relationships. J Proteome Res. 2015;14(2):1220–1237.
   PubMed Web of Science ®Google Scholar
• Garcia CJ, Khajeh J, Coulanges E, et al. Regulation of mitochondrial complex I biogenesis in Drosophila flight muscles. Cell Rep. 2017;20(1):264–278.
   PubMed Web of Science ®Google Scholar
• Aebersold R, Mann M. Mass-spectrometric exploration of proteome structure and function. Nature. 2016;537(7620):347–355.
   PubMed Web of Science ®Google Scholar
• Lundberg E, Borner GHH. Spatial proteomics: a powerful discovery tool for cell biology. Nat Rev Mol Cell Biol. 2019;20(5):285–302.
   PubMed Web of Science ®Google Scholar
• Thul PJ, Akesson L, Wiking M, et al. A subcellular map of the human proteome. Science. 2017; 356(6340):eaal3321.
   PubMed Web of Science ®Google Scholar
• Uhlen M, Fagerberg L, Hallstrom BM, et al. Proteomics. Tissue-based map of the human proteome. Science. 2015;347(6220):1260419.
   PubMed Web of Science ®Google Scholar
• Cereghetti GM, Stangherlin A, Martins de Brito O, et al. Dephosphorylation by calcineurin regulates translocation of Drp1 to mitochondria. Proc Natl Acad Sci U S A. 2008;105(41):15803–15808.
   PubMed Web of Science ®Google Scholar
• Cribbs JT, Strack S. Reversible phosphorylation of Drp1 by cyclic AMP-dependent protein kinase and calcineurin regulates mitochondrial fission and cell death. EMBO Rep. 2007;8(10):939–944.
   PubMed Web of Science ®Google Scholar
• Hirabayashi Y, Kwon S-K, Paek H, et al. ER-mitochondria tethering by PDZD8 regulates Ca2+ dynamics in mammalian neurons. Science. 2017;358(6363):623–630.
   PubMed Web of Science ®Google Scholar
• Gomez-Serrano M, Camafeita E, Loureiro M, et al. Tackling mitochondrial dysfunction in human disease. Oxid Med Cell Longev. 2018;2018:1435934.
   PubMed Web of Science ®Google Scholar
• Basso V, Marchesan E, Peggion C, et al. Regulation of ER-mitochondria contacts by Parkin via Mfn2. Pharmacol Res. 2018;138:43–56.
   PubMed Web of Science ®Google Scholar
• Calvo SE, Mootha VK. The mitochondrial proteome and human disease. Annu Rev Genomics Hum Genet. 2010;11:25–44.
   PubMed Web of Science ®Google Scholar
• Smith AC, Robinson AJ. MitoMiner v4.0: an updated database of mitochondrial localization evidence, phenotypes and diseases. Nucleic Acids Res. 2019;47(D1):D1225–D1228.
   PubMed Web of Science ®Google Scholar
• Calvo SE, Clauser KR, Mootha VK. MitoCarta2.0: an updated inventory of mammalian mitochondrial proteins. Nucleic Acids Res. 2016;44(D1):D1251–1257.
   PubMed Web of Science ®Google Scholar
• UniProt C. UniProt: a worldwide hub of protein knowledge. Nucleic Acids Res. 2019;47(D1):D506–D515.
   PubMed Web of Science ®Google Scholar
• Maere S, Heymans K, Kuiper M. BiNGO: a cytoscape plugin to assess overrepresentation of gene ontology categories in biological networks. Bioinformatics. 2005;21(16):3448–3449.
   PubMed Web of Science ®Google Scholar
• Malty RH, Aoki H, Kumar A, et al. A map of human mitochondrial protein interactions linked to neurodegeneration reveals new mechanisms of redox homeostasis and NF-kappaB signaling. Cell Syst. 2017;5(6):564–577 e512.
   PubMed Web of Science ®Google Scholar
• Moutaoufik MT, Malty R, Amin S, et al. Rewiring of the human mitochondrial interactome during neuronal reprogramming reveals regulators of the respirasome and neurogenesis. iScience. 2019;19:1114–1132.
   PubMed Web of Science ®Google Scholar
• Huttlin EL, Bruckner RJ, Paulo JA, et al. Architecture of the human interactome defines protein communities and disease networks. Nature. 2017;545(7655):505–509.
   PubMed Web of Science ®Google Scholar
• Havugimana PC, Hart GT, Nepusz T, et al. A census of human soluble protein complexes. Cell. 2012;150(5):1068–1081.
   PubMed Web of Science ®Google Scholar
• Wan C, Borgeson B, Phanse S, et al. Panorama of ancient metazoan macromolecular complexes. Nature. 2015;525(7569):339–344.
   PubMed Web of Science ®Google Scholar
• Hein MY, Hubner NC, Poser I, et al. A human interactome in three quantitative dimensions organized by stoichiometries and abundances. Cell. 2015;163(3):712–723.
   PubMed Web of Science ®Google Scholar
• Floyd BJ, Wilkerson EM, Veling MT, et al. Mitochondrial protein interaction mapping identifies regulators of respiratory chain function. Mol Cell. 2016;63(4):621–632.
   PubMed Web of Science ®Google Scholar
• Gagarinova A, Phanse S, Cygler M, et al. Insights from protein-protein interaction studies on bacterial pathogenesis. Expert Rev Proteomics. 2017;14(9):779–797.
   PubMed Web of Science ®Google Scholar
• Liu X, Salokas K, Tamene F, et al. An AP-MS- and BioID-compatible MAC-tag enables comprehensive mapping of protein interactions and subcellular localizations. Nat Commun. 2018;9(1):1188.
   PubMedGoogle Scholar
• Hung V, Zou P, HW R, et al. Proteomic mapping of the human mitochondrial intermembrane space in live cells via ratiometric APEX tagging. Mol Cell. 2014;55(2):332–341.
   PubMed Web of Science ®Google Scholar
• Branon TC, Bosch JA, Sanchez AD, et al. Efficient proximity labeling in living cells and organisms with TurboID. Nat Biotechnol. 2018;36(9):880–887.
   PubMed Web of Science ®Google Scholar
• Gingras AC, Abe KT, Raught B. Getting to know the neighborhood: using proximity-dependent biotinylation to characterize protein complexes and map organelles. Curr Opin Chem Biol. 2019;48:44–54.
   PubMed Web of Science ®Google Scholar
• Sahni N, Yi S, Taipale M, et al. Widespread macromolecular interaction perturbations in human genetic disorders. Cell. 2015;161(3):647–660.
   PubMed Web of Science ®Google Scholar
• Gavin AC, Aloy P, Grandi P, et al. Proteome survey reveals modularity of the yeast cell machinery. Nature. 2006;440(7084):631–636.
   PubMed Web of Science ®Google Scholar
• Aloy P, Bottcher B, Ceulemans H, et al. Structure-based assembly of protein complexes in yeast. Science. 2004;303(5666):2026–2029.
   PubMed Web of Science ®Google Scholar
• Aloy P, Russell RB. Interrogating protein interaction networks through structural biology. Proc Natl Acad Sci U S A. 2002;99(9):5896–5901.
   PubMed Web of Science ®Google Scholar
• Mosca R, Ceol A, Aloy P. Interactome3D: adding structural details to protein networks. Nat Methods. 2013;10(1):47–53.
   PubMed Web of Science ®Google Scholar
• Rolland T, Tasan M, Charloteaux B, et al. A proteome-scale map of the human interactome network. Cell. 2014;159(5):1212–1226.
   PubMed Web of Science ®Google Scholar
• Rajagopala SV, Sikorski P, Kumar A, et al. The binary protein-protein interaction landscape of Escherichia coli. Nat Biotechnol. 2014;32(3):285–290.
   PubMed Web of Science ®Google Scholar
• Mosca R, Tenorio-Laranga J, Olivella R, et al. dSysMap: exploring the edgetic role of disease mutations. Nat Methods. 2015;12(3):167–168.
   PubMed Web of Science ®Google Scholar
• Miquel Duran-Frigola EP, Guitart-Pla O, Bertoni M, et al. Extending the small molecule similarity principle to all levels of biology. bioRxiv. 2019.DOI: https://doi.org/10.1101/745703
   Google Scholar
• Picart-Armada S, Barrett SJ, Wille DR, et al. Benchmarking network propagation methods for disease gene identification. PLoS Comput Biol. 2019;15(9):e1007276.
   PubMed Web of Science ®Google Scholar
• Drew K, Muller CL, Bonneau R, et al. Identifying direct contacts between protein complex subunits from their conditional dependence in proteomics datasets. PLoS Comput Biol. 2017;13(10):e1005625.
   PubMed Web of Science ®Google Scholar
• Misgeld T, Schwarz TL. Mitostasis in neurons: maintaining mitochondria in an extended cellular architecture. Neuron. 2017;96(3):651–666.
   PubMed Web of Science ®Google Scholar
• Zhu T, Chen JL, Wang Q, et al. Modulation of mitochondrial dynamics in neurodegenerative diseases: an insight into prion diseases. Front Aging Neurosci. 2018;10:336.
   PubMed Web of Science ®Google Scholar
• Pernas L, Mito-Morphosis: SL, Fusion M. Fission, and cristae remodeling as key mediators of cellular function. Annu Rev Physiol. 2016;78:505–531.
   PubMed Web of Science ®Google Scholar
• Klecker T, Wemmer M, Haag M, et al. Interaction of MDM33 with mitochondrial inner membrane homeostasis pathways in yeast. Sci Rep. 2015;5:18344.
   PubMed Web of Science ®Google Scholar
• Lewis SC, Uchiyama LF, Nunnari J. ER-mitochondria contacts couple mtDNA synthesis with mitochondrial division in human cells. Science. 2016;353(6296):aaf5549.
   PubMed Web of Science ®Google Scholar
• Murley A, Lackner LL, Osman C, et al. ER-associated mitochondrial division links the distribution of mitochondria and mitochondrial DNA in yeast. Elife. 2013;2:e00422.
   PubMed Web of Science ®Google Scholar
• Filadi R, Pendin D, Pizzo P. Mitofusin 2: from functions to disease. Cell Death Dis. 2018;9(3):330.
   PubMedGoogle Scholar
• Misko A, Jiang S, Wegorzewska I, et al. Mitofusin 2 is necessary for transport of axonal mitochondria and interacts with the Miro/Milton complex. J Neurosci. 2010;30(12):4232–4240.
   PubMed Web of Science ®Google Scholar
• Sheng ZH, Cai Q. Mitochondrial transport in neurons: impact on synaptic homeostasis and neurodegeneration. Nat Rev Neurosci. 2012;13(2):77–93.
   PubMed Web of Science ®Google Scholar
• MacVicar T, Langer T. OPA1 processing in cell death and disease - the long and short of it. J Cell Sci. 2016;129(12):2297–2306.
   PubMed Web of Science ®Google Scholar
• Cipolat S, Rudka T, Hartmann D, et al. Mitochondrial rhomboid PARL regulates cytochrome c release during apoptosis via OPA1-dependent cristae remodeling. Cell. 2006;126(1):163–175.
   PubMed Web of Science ®Google Scholar
• Ishihara N, Fujita Y, Oka T, et al. Regulation of mitochondrial morphology through proteolytic cleavage of OPA1. Embo J. 2006;25(13):2966–2977.
   PubMed Web of Science ®Google Scholar
• Twig G, Elorza A, Molina AJ, et al. Fission and selective fusion govern mitochondrial segregation and elimination by autophagy. Embo J. 2008;27(2):433–446.
   PubMed Web of Science ®Google Scholar
• Shirihai OS, Song M, Dorn GW 2nd. How mitochondrial dynamism orchestrates mitophagy. Circ Res. 2015;116(11):1835–1849.
   PubMed Web of Science ®Google Scholar
• Kornfeld OS, Hwang S, Disatnik MH, et al. Mitochondrial reactive oxygen species at the heart of the matter: new therapeutic approaches for cardiovascular diseases. Circ Res. 2015;116(11):1783–1799.
   PubMed Web of Science ®Google Scholar
• Zhang Z, Liu L, Wu S, et al. Drp1, Mff, Fis1, and MiD51 are coordinated to mediate mitochondrial fission during UV irradiation-induced apoptosis. Faseb J. 2016;30(1):466–476.
   PubMed Web of Science ®Google Scholar
• Prudent J, Zunino R, Sugiura A, et al. MAPL Sumoylation of Drp1 Stabilizes an ER/mitochondrial platform required for cell death. Mol Cell. 2015;59(6):941–955.
   PubMed Web of Science ®Google Scholar
• Lee KS, Lu B. The myriad roles of Miro in the nervous system: axonal transport of mitochondria and beyond. Front Cell Neurosci. 2014;8:330.
   PubMed Web of Science ®Google Scholar
• Melkov A, Abdu U. Regulation of long-distance transport of mitochondria along microtubules. Cell Mol Life Sci. 2018;75(2):163–176.
   PubMed Web of Science ®Google Scholar
• Course MM, Wang X. Transporting mitochondria in neurons. F1000Res. 2016;5:1735.
   PubMedGoogle Scholar
• Harris JJ, Jolivet R, Attwell D. Synaptic energy use and supply. Neuron. 2012;75(5):762–777.
   PubMed Web of Science ®Google Scholar
• AD P, Horiuchi D, CM L, et al. Kinesin-1 and Dynein are the primary motors for fast transport of mitochondria in Drosophila motor axons. Mol Biol Cell. 2006;17(4):2057–2068.
   PubMed Web of Science ®Google Scholar
• Saxton WM, Hollenbeck PJ. The axonal transport of mitochondria. J Cell Sci. 2012;125(Pt 9):2095–2104.
   PubMed Web of Science ®Google Scholar
• Gureev AP, Shaforostova EA, Popov VN. Regulation of mitochondrial biogenesis as a way for active longevity: interaction between the Nrf2 and PGC-1alpha signaling pathways. Front Genet. 2019;10:435.
   PubMed Web of Science ®Google Scholar
• Yasukawa T, Kang D. An overview of mammalian mitochondrial DNA replication mechanisms. J Biochem. 2018;164(3):183–193.
   PubMed Web of Science ®Google Scholar
• Nisoli E, Falcone S, Tonello C, et al. Mitochondrial biogenesis by NO yields functionally active mitochondria in mammals. Proc Natl Acad Sci U S A. 2004;101(47):16507–16512.
   PubMed Web of Science ®Google Scholar
• Sun Y, Vashisht AA, Tchieu J, et al. Voltage-dependent anion channels (VDACs) recruit Parkin to defective mitochondria to promote mitochondrial autophagy. J Biol Chem. 2012;287(48):40652–40660.
   PubMed Web of Science ®Google Scholar
• Chen Y, Dorn GW 2nd. PINK1-phosphorylated mitofusin 2 is a Parkin receptor for culling damaged mitochondria. Science. 2013;340(6131):471–475.
   PubMed Web of Science ®Google Scholar
• Sarraf SA, Raman M, Guarani-Pereira V, et al. Landscape of the PARKIN-dependent ubiquitylome in response to mitochondrial depolarization. Nature. 2013;496(7445):372–376.
   PubMed Web of Science ®Google Scholar
• Sekine S, Wang C, Sideris DP, et al. Reciprocal roles of Tom7 and OMA1 during mitochondrial import and activation of PINK1. Mol Cell. 2019;73(5):1028–1043 e1025.
   PubMed Web of Science ®Google Scholar
• Blackinton J, Lakshminarasimhan M, Thomas KJ, et al. Formation of a stabilized cysteine sulfinic acid is critical for the mitochondrial function of the parkinsonism protein DJ-1. J Biol Chem. 2009;284(10):6476–6485.
   PubMed Web of Science ®Google Scholar
• Krebiehl G, Ruckerbauer S, Burbulla LF, et al. Reduced basal autophagy and impaired mitochondrial dynamics due to loss of Parkinson’s disease-associated protein DJ-1. PLoS One. 2010;5(2):e9367.
   PubMed Web of Science ®Google Scholar
• Fimia GM, Stoykova A, Romagnoli A, et al. Ambra1 regulates autophagy and development of the nervous system. Nature. 2007;447(7148):1121–1125.
   PubMed Web of Science ®Google Scholar
• Yamada T, Dawson TM, Yanagawa T, et al. SQSTM1/p62 promotes mitochondrial ubiquitination independently of PINK1 and PRKN/parkin in mitophagy. Autophagy. 2019;15(11):2012–2018.
   PubMed Web of Science ®Google Scholar
• Lee Y, Lee HY, Hanna RA, et al. Mitochondrial autophagy by Bnip3 involves Drp1-mediated mitochondrial fission and recruitment of Parkin in cardiac myocytes. Am J Physiol Heart Circ Physiol. 2011;301(5):H1924–1931.
   PubMed Web of Science ®Google Scholar
• Bellot G, Garcia-Medina R, Gounon P, et al. Hypoxia-induced autophagy is mediated through hypoxia-inducible factor induction of BNIP3 and BNIP3L via their BH3 domains. Mol Cell Biol. 2009;29(10):2570–2581.
   PubMed Web of Science ®Google Scholar
• Yamano K, Wang C, Sarraf SA, et al. Endosomal Rab cycles regulate Parkin-mediated mitophagy. Elife. 2018;7:e31326.
   Web of Science ®Google Scholar
• Hammerling BC, Najor RH, Cortez MQ, et al. A Rab5 endosomal pathway mediates Parkin-dependent mitochondrial clearance. Nat Commun. 2017;8:14050.
   PubMed Web of Science ®Google Scholar
• Yamano K, Fogel AI, Wang C, et al. Mitochondrial rab GAPs govern autophagosome biogenesis during mitophagy. Elife. 2014;3:e01612.
   PubMed Web of Science ®Google Scholar
• Tatsuta T. Protein quality control in mitochondria. J Biochem. 2009;146(4):455–461.
   PubMed Web of Science ®Google Scholar
• Livnat-Levanon N, Glickman MH. Ubiquitin-proteasome system and mitochondria - reciprocity. Biochim Biophys Acta. 2011;1809(2):80–87.
   PubMed Web of Science ®Google Scholar
• Pickrell AM, Youle RJ. The roles of PINK1, parkin, and mitochondrial fidelity in Parkinson’s disease. Neuron. 2015;85(2):257–273.
   PubMed Web of Science ®Google Scholar
• Stevens DA, Lee Y, Kang HC, et al. Parkin loss leads to PARIS-dependent declines in mitochondrial mass and respiration. Proc Natl Acad Sci U S A. 2015;112(37):11696–11701.
   PubMed Web of Science ®Google Scholar
• Lee Y, Stevens DA, Kang SU, et al. PINK1 primes parkin-mediated ubiquitination of PARIS in dopaminergic neuronal survival. Cell Rep. 2017;18(4):918–932.
   PubMed Web of Science ®Google Scholar
• Roberts RF, Tang MY, Fon EA, et al. Defending the mitochondria: the pathways of mitophagy and mitochondrial-derived vesicles. Int J Biochem Cell Biol. 2016;79:427–436.
   PubMed Web of Science ®Google Scholar
• Matheoud D, Sugiura A, Bellemare-Pelletier A, et al. Parkinson’s disease-related proteins PINK1 and parkin repress mitochondrial antigen presentation. Cell. 2016;166(2):314–327.
   PubMed Web of Science ®Google Scholar
• Flippo KH, Strack S. Mitochondrial dynamics in neuronal injury, development and plasticity. J Cell Sci. 2017;130(4):671–681.
   PubMed Web of Science ®Google Scholar
• Reeve AK, Grady JP, Cosgrave EM, et al. Mitochondrial dysfunction within the synapses of substantia nigra neurons in Parkinson’s disease. NPJ Parkinsons Dis. 2018;4:9.
   PubMed Web of Science ®Google Scholar
• Zorzano A, Claret M. Implications of mitochondrial dynamics on neurodegeneration and on hypothalamic dysfunction. Front Aging Neurosci. 2015;7:101.
   PubMed Web of Science ®Google Scholar
• Gibbs RM, Lipnick S, Bateman JW, et al. Toward precision medicine for neurological and neuropsychiatric disorders. Cell Stem Cell. 2018;23(1):21–24.
   PubMed Web of Science ®Google Scholar
• Kalman S, Garbett KA, Janka Z, et al. Human dermal fibroblasts in psychiatry research. Neuroscience. 2016;320:105–121.
   PubMed Web of Science ®Google Scholar
• Auburger G, Klinkenberg M, Drost J, et al. Primary skin fibroblasts as a model of Parkinson’s disease. Mol Neurobiol. 2012;46(1):20–27.
   PubMed Web of Science ®Google Scholar
• Lundgaard I, Osorio MJ, Kress BT, et al. White matter astrocytes in health and disease. Neuroscience. 2014;276:161–173.
   PubMed Web of Science ®Google Scholar
• Yellen G. Fueling thought: management of glycolysis and oxidative phosphorylation in neuronal metabolism. J Cell Biol. 2018;217(7):2235–2246.
   PubMed Web of Science ®Google Scholar
• Lemons JM, Feng XJ, Bennett BD, et al. Quiescent fibroblasts exhibit high metabolic activity. PLoS Biol. 2010;8(10):e1000514.
   PubMed Web of Science ®Google Scholar
• Takano T, Funahashi Y, Neuronal Polarity: KK. Positive and negative feedback signals. Front Cell Dev Biol. 2019;7:69.
   PubMed Web of Science ®Google Scholar
• Glaros T, Larsen M, Li L. Macrophages and fibroblasts during inflammation, tissue damage and organ injury. Front Biosci (Landmark Ed). 2009;14:3988–3993.
   PubMed Web of Science ®Google Scholar
• Kang S, Chen X, Gong S, et al. Characteristic analyses of a neural differentiation model from iPSC-derived neuron according to morphology, physiology, and global gene expression pattern. Sci Rep. 2017;7(1):12233.
   PubMedGoogle Scholar
• Shi Y, Inoue H, Wu JC, et al. Induced pluripotent stem cell technology: a decade of progress. Nat Rev Drug Discov. 2017;16(2):115–130.
   PubMed Web of Science ®Google Scholar
• Corrales NL, Mrasek K, Voigt M, et al. Copy number variations (CNVs) in human pluripotent cell-derived neuroprogenitors. Gene. 2012;506(2):377–379.
   PubMed Web of Science ®Google Scholar
• Belinsky GS, Rich MT, Sirois CL, et al. Patch-clamp recordings and calcium imaging followed by single-cell PCR reveal the developmental profile of 13 genes in iPSC-derived human neurons. Stem Cell Res. 2014;12(1):101–118.
   PubMed Web of Science ®Google Scholar
• Lang C, Campbell KR, Ryan BJ, et al. Single-cell sequencing of iPSC-dopamine neurons reconstructs disease progression and identifies HDAC4 as a regulator of parkinson cell phenotypes. Cell Stem Cell. 2019;24(1):93–106 e106.
   PubMed Web of Science ®Google Scholar
• Bowles KR, Tcw J, Qian L, et al. Reduced variability of neural progenitor cells and improved purity of neuronal cultures using magnetic activated cell sorting. PLoS One. 2019;14(3):e0213374.
   PubMed Web of Science ®Google Scholar
• Qian X, Song H, Ming GL. Brain organoids: advances, applications and challenges. Development. 2019;146(8):dev166074.
   Web of Science ®Google Scholar
• Di Lullo E, Kriegstein AR. The use of brain organoids to investigate neural development and disease. Nat Rev Neurosci. 2017;18(10):573–584.
   PubMed Web of Science ®Google Scholar
• Quadrato G, Nguyen T, Macosko EZ, et al. Cell diversity and network dynamics in photosensitive human brain organoids. Nature. 2017;545(7652):48–53.
   PubMed Web of Science ®Google Scholar
• Bogetofte H, Jensen P, Ryding M, et al. PARK2 mutation causes metabolic disturbances and impaired survival of human iPSC-derived neurons. Front Cell Neurosci. 2019;13:297.
   PubMed Web of Science ®Google Scholar
• Sala Frigerio C, Wolfs L, Fattorelli N, et al. The major risk factors for Alzheimer’s disease: age, sex, and genes modulate the microglia response to abeta plaques. Cell Rep. 2019;27(4):1293–1306 e1296.
   PubMed Web of Science ®Google Scholar
• Zucca S, Gagliardi S, Pandini C, et al. RNA-Seq profiling in peripheral blood mononuclear cells of amyotrophic lateral sclerosis patients and controls. Sci Data. 2019;6:190006.
   PubMed Web of Science ®Google Scholar
• Hu W, Wang Z, Zheng H. Mitochondrial accumulation of amyloid beta (Abeta) peptides requires TOMM22 as a main Abeta receptor in yeast. J Biol Chem. 2018;293(33):12681–12689.
   PubMed Web of Science ®Google Scholar
• Shahmoradian SH, Lewis AJ, Genoud C, et al. Lewy pathology in Parkinson’s disease consists of crowded organelles and lipid membranes. Nat Neurosci. 2019;22(7):1099–1109.
   PubMed Web of Science ®Google Scholar
• Balasubramaniam M, Ayyadevara S, Ganne A, et al. Aggregate interactome based on protein cross-linking interfaces predicts drug targets to limit aggregation in neurodegenerative diseases. iScience. 2019;20:248–264.
   PubMed Web of Science ®Google Scholar
• Pinero J, Bravo A, Queralt-Rosinach N, et al. DisGeNET: a comprehensive platform integrating information on human disease-associated genes and variants. Nucleic Acids Res. 2017;45(D1):D833–D839.
   PubMed Web of Science ®Google Scholar
• Crichton G, Guo Y, Pyysalo S, et al. Neural networks for link prediction in realistic biomedical graphs: a multi-dimensional evaluation of graph embedding-based approaches. BMC Bioinformatics. 2018;19(1):176.
   PubMedGoogle Scholar
• Tsuda M, Asano S, Kato Y, et al. Differential diagnosis of multiple system atrophy with predominant parkinsonism and Parkinson’s disease using neural networks. J Neurol Sci. 2019;401:19–26.
   PubMed Web of Science ®Google Scholar
• Lashuel HA, Overk CR, Oueslati A, et al. The many faces of alpha-synuclein: from structure and toxicity to therapeutic target. Nat Rev Neurosci. 2013;14(1):38–48.
   PubMed Web of Science ®Google Scholar
• Devi L, Raghavendran V, Prabhu BM, et al. Mitochondrial import and accumulation of alpha-synuclein impair complex I in human dopaminergic neuronal cultures and Parkinson disease brain. J Biol Chem. 2008;283(14):9089–9100.
   PubMed Web of Science ®Google Scholar
• Pozo Devoto VM, Dimopoulos N, Alloatti M, et al. alphaSynuclein control of mitochondrial homeostasis in human-derived neurons is disrupted by mutations associated with Parkinson’s disease. Sci Rep. 2017;7(1):5042.
   PubMedGoogle Scholar
• Xie W, Chung KK. Alpha-synuclein impairs normal dynamics of mitochondria in cell and animal models of Parkinson’s disease. J Neurochem. 2012;122(2):404–414.
   PubMed Web of Science ®Google Scholar
• Nakamura K, Nemani VM, Azarbal F, et al. Direct membrane association drives mitochondrial fission by the Parkinson disease-associated protein alpha-synuclein. J Biol Chem. 2011;286(23):20710–20726.
   PubMed Web of Science ®Google Scholar
• Volpicelli-Daley LA, Gamble KL, Schultheiss CE, et al. Formation of alpha-synuclein Lewy neurite-like aggregates in axons impedes the transport of distinct endosomes. Mol Biol Cell. 2014;25(25):4010–4023.
   PubMed Web of Science ®Google Scholar
• Prots I, Veber V, Brey S, et al. alpha-Synuclein oligomers impair neuronal microtubule-kinesin interplay. J Biol Chem. 2013;288(30):21742–21754.
   PubMed Web of Science ®Google Scholar
• Utton MA, Noble WJ, Hill JE, et al. Molecular motors implicated in the axonal transport of tau and alpha-synuclein. J Cell Sci. 2005;118(Pt 20):4645–4654.
   PubMed Web of Science ®Google Scholar
• Meng H, Yamashita C, Shiba-Fukushima K, et al. Loss of Parkinson’s disease-associated protein CHCHD2 affects mitochondrial crista structure and destabilizes cytochrome c. Nat Commun. 2017;8:15500.
   PubMed Web of Science ®Google Scholar
• Aras S, Bai M, Lee I, et al. MNRR1 (formerly CHCHD2) is a bi-organellar regulator of mitochondrial metabolism. Mitochondrion. 2015;20:43–51.
   PubMed Web of Science ®Google Scholar
• Baughman JM, Nilsson R, Gohil VM, et al. A computational screen for regulators of oxidative phosphorylation implicates SLIRP in mitochondrial RNA homeostasis. PLoS Genet. 2009;5(8):e1000590.
   PubMed Web of Science ®Google Scholar
• Stafa K, Tsika E, Moser R, et al. Functional interaction of Parkinson’s disease-associated LRRK2 with members of the dynamin GTPase superfamily. Hum Mol Genet. 2014;23(8):2055–2077.
   PubMed Web of Science ®Google Scholar
• Wang X, Yan MH, Fujioka H, et al. LRRK2 regulates mitochondrial dynamics and function through direct interaction with DLP1. Hum Mol Genet. 2012;21(9):1931–1944.
   PubMed Web of Science ®Google Scholar
• Perez Carrion M, Pischedda F, Biosa A, et al. The LRRK2 variant E193K prevents mitochondrial fission upon MPP+ treatment by altering LRRK2 binding to DRP1. Front Mol Neurosci. 2018;11:64.
   PubMed Web of Science ®Google Scholar
• Niu J, Yu M, Wang C, et al. Leucine-rich repeat kinase 2 disturbs mitochondrial dynamics via dynamin-like protein. J Neurochem. 2012;122(3):650–658.
   PubMed Web of Science ®Google Scholar
• Su YC, Qi X. Inhibition of excessive mitochondrial fission reduced aberrant autophagy and neuronal damage caused by LRRK2 G2019S mutation. Hum Mol Genet. 2013;22(22):4545–4561.
   PubMed Web of Science ®Google Scholar
• Caesar M, Zach S, Carlson CB, et al. Leucine-rich repeat kinase 2 functionally interacts with microtubules and kinase-dependently modulates cell migration. Neurobiol Dis. 2013;54:280–288.
   PubMed Web of Science ®Google Scholar
• Melrose HL, Dachsel JC, Behrouz B, et al. Impaired dopaminergic neurotransmission and microtubule-associated protein tau alterations in human LRRK2 transgenic mice. Neurobiol Dis. 2010;40(3):503–517.
   PubMed Web of Science ®Google Scholar
• Hsieh CH, Shaltouki A, Gonzalez AE, et al. Functional impairment in miro degradation and mitophagy is a shared feature in familial and sporadic Parkinson’s disease. Cell Stem Cell. 2016;19(6):709–724.
   PubMed Web of Science ®Google Scholar
• Su YC, Guo X, Threonine QX. 56 phosphorylation of Bcl-2 is required for LRRK2 G2019S-induced mitochondrial depolarization and autophagy. Biochim Biophys Acta. 2015;1852(1):12–21.
   PubMed Web of Science ®Google Scholar
• Pryde KR, Smith HL, Chau KY, et al. PINK1 disables the anti-fission machinery to segregate damaged mitochondria for mitophagy. J Cell Biol. 2016;213(2):163–171.
   PubMed Web of Science ®Google Scholar
• Zanellati MC, Monti V, Barzaghi C, et al. Mitochondrial dysfunction in Parkinson disease: evidence in mutant PARK2 fibroblasts. Front Genet. 2015;6:78.
   PubMed Web of Science ®Google Scholar
• Poole AC, Thomas RE, Andrews LA, et al. The PINK1/Parkin pathway regulates mitochondrial morphology. Proc Natl Acad Sci U S A. 2008;105(5):1638–1643.
   PubMed Web of Science ®Google Scholar
• Yang Y, Ouyang Y, Yang L, et al. Pink1 regulates mitochondrial dynamics through interaction with the fission/fusion machinery. Proc Natl Acad Sci U S A. 2008;105(19):7070–7075.
   PubMed Web of Science ®Google Scholar
• Smith EF, Shaw PJ, De Vos KJ. The role of mitochondria in amyotrophic lateral sclerosis. Neurosci Lett. 2019;710:132933.
   PubMed Web of Science ®Google Scholar
• Israelson A, Arbel N, Da Cruz S, et al. Misfolded mutant SOD1 directly inhibits VDAC1 conductance in a mouse model of inherited ALS. Neuron. 2010;67(4):575–587.
   PubMed Web of Science ®Google Scholar
• Moller A, Bauer CS, Cohen RN, et al. Amyotrophic lateral sclerosis-associated mutant SOD1 inhibits anterograde axonal transport of mitochondria by reducing Miro1 levels. Hum Mol Genet. 2017;26(23):4668–4679.
   PubMed Web of Science ®Google Scholar
• Chen Y, Deng J, Wang P, et al. PINK1 and Parkin are genetic modifiers for FUS-induced neurodegeneration. Hum Mol Genet. 2016;25(23):5059–5068.
   PubMed Web of Science ®Google Scholar
• Deng J, Yang M, Chen Y, et al. FUS interacts with HSP60 to promote mitochondrial damage. PLoS Genet. 2015;11(9):e1005357.
   PubMed Web of Science ®Google Scholar
• Wang W, Wang L, Lu J, et al. The inhibition of TDP-43 mitochondrial localization blocks its neuronal toxicity. Nat Med. 2016;22(8):869–878.
   PubMed Web of Science ®Google Scholar
• Davis SA, Itaman S, Khalid-Janney CM, et al. TDP-43 interacts with mitochondrial proteins critical for mitophagy and mitochondrial dynamics. Neurosci Lett. 2018;678:8–15.
   PubMed Web of Science ®Google Scholar
• Stoica R, De Vos KJ, Paillusson S, et al. ER-mitochondria associations are regulated by the VAPB-PTPIP51 interaction and are disrupted by ALS/FTD-associated TDP-43. Nat Commun. 2014;5:3996.
   PubMed Web of Science ®Google Scholar
• Baldwin KR, Godena VK, Hewitt VL, et al. Axonal transport defects are a common phenotype in Drosophila models of ALS. Hum Mol Genet. 2016;25(12):2378–2392.
   PubMed Web of Science ®Google Scholar
• Joshi AU, Saw NL, Vogel H, et al. Inhibition of Drp1/Fis1 interaction slows progression of amyotrophic lateral sclerosis. EMBO Mol Med. 2018;10:3.
   Web of Science ®Google Scholar
• Weil R, Laplantine E, Curic S, et al. Role of optineurin in the mitochondrial dysfunction: potential implications in neurodegenerative diseases and cancer. Front Immunol. 2018;9:1243.
   PubMed Web of Science ®Google Scholar
• Goode A, Butler K, Long J, et al. Defective recognition of LC3B by mutant SQSTM1/p62 implicates impairment of autophagy as a pathogenic mechanism in ALS-FTLD. Autophagy. 2016;12(7):1094–1104.
   PubMed Web of Science ®Google Scholar
• Kim NC, Tresse E, Kolaitis RM, et al. VCP is essential for mitochondrial quality control by PINK1/Parkin and this function is impaired by VCP mutations. Neuron. 2013;78(1):65–80.
   PubMed Web of Science ®Google Scholar
• Soler-Lopez M, Zanzoni A, Lluis R, et al. Interactome mapping suggests new mechanistic details underlying Alzheimer’s disease. Genome Res. 2011;21(3):364–376.
   PubMed Web of Science ®Google Scholar
• Hansson Petersen CA, Alikhani N, Behbahani H, et al. The amyloid beta-peptide is imported into mitochondria via the TOM import machinery and localized to mitochondrial cristae. Proc Natl Acad Sci U S A. 2008;105(35):13145–13150.
   PubMed Web of Science ®Google Scholar
• Sirk D, Zhu Z, Wadia JS, et al. Chronic exposure to sub-lethal beta-amyloid (Abeta) inhibits the import of nuclear-encoded proteins to mitochondria in differentiated PC12 cells. J Neurochem. 2007;103(5):1989–2003.
   PubMed Web of Science ®Google Scholar
• Fernandez-Echevarria C, Diaz M, Ferrer I, et al. Abeta promotes VDAC1 channel dephosphorylation in neuronal lipid rafts. Relevance to the mechanisms of neurotoxicity in Alzheimer’s disease. Neuroscience. 2014;278:354–366.
   PubMed Web of Science ®Google Scholar
• Manczak M, Reddy PH. Abnormal interaction of VDAC1 with amyloid beta and phosphorylated tau causes mitochondrial dysfunction in Alzheimer’s disease. Hum Mol Genet. 2012;21(23):5131–5146.
   PubMed Web of Science ®Google Scholar
• Du H, Guo L, Fang F, et al. Cyclophilin D deficiency attenuates mitochondrial and neuronal perturbation and ameliorates learning and memory in Alzheimer’s disease. Nat Med. 2008;14(10):1097–1105.
   PubMed Web of Science ®Google Scholar
• Lustbader JW, Cirilli M, Lin C, et al. ABAD directly links Abeta to mitochondrial toxicity in Alzheimer’s disease. Science. 2004;304(5669):448–452.
   PubMed Web of Science ®Google Scholar
• LaPointe NE, Morfini G, Pigino G, et al. The amino terminus of tau inhibits kinesin-dependent axonal transport: implications for filament toxicity. J Neurosci Res. 2009;87(2):440–451.
   PubMed Web of Science ®Google Scholar
• Ittner LM, Ke YD, Gotz J. Phosphorylated Tau interacts with c-Jun N-terminal kinase-interacting protein 1 (JIP1) in Alzheimer disease. J Biol Chem. 2009;284(31):20909–20916.
   PubMed Web of Science ®Google Scholar
• Corsetti V, Florenzano F, Atlante A, et al. NH2-truncated human tau induces deregulated mitophagy in neurons by aberrant recruitment of Parkin and UCHL-1: implications in Alzheimer’s disease. Hum Mol Genet. 2015;24(11):3058–3081.
   PubMed Web of Science ®Google Scholar
• Cummins N, Tweedie A, Zuryn S, et al. Disease-associated tau impairs mitophagy by inhibiting Parkin translocation to mitochondria. Embo J. 2019;38:3.
   Web of Science ®Google Scholar
• Di Domenico F, Sultana R, Barone E, et al. Quantitative proteomics analysis of phosphorylated proteins in the hippocampus of Alzheimer’s disease subjects. J Proteomics. 2011;74(7):1091–1103.
   PubMed Web of Science ®Google Scholar
• Zahid S, Oellerich M, Asif AR, et al. Phosphoproteome profiling of substantia nigra and cortex regions of Alzheimer’s disease patients. J Neurochem. 2012;121(6):954–963.
   PubMed Web of Science ®Google Scholar
• Wu Y, Chen M, Jiang J. Mitochondrial dysfunction in neurodegenerative diseases and drug targets via apoptotic signaling. Mitochondrion. 2019;49:35–45.
   PubMed Web of Science ®Google Scholar
• Wang Y, An H, Liu T, et al. Metformin improves mitochondrial respiratory activity through activation of AMPK. Cell Rep. 2019;29(6):1511–1523 e1515.
   PubMed Web of Science ®Google Scholar
• Lee J, Kim CH, Simon DK, et al. Mitochondrial cyclic AMP response element-binding protein (CREB) mediates mitochondrial gene expression and neuronal survival. J Biol Chem. 2005;280(49):40398–40401.
   PubMed Web of Science ®Google Scholar
• Wang W, Fujii H, Kim HJ, et al. Enhanced human hematopoietic stem and progenitor cell engraftment by blocking donor T cell-mediated TNFalpha signaling. Sci Transl Med. 2017;9(421):eaag3214.
   Web of Science ®Google Scholar
• Carrillo O, Laughton CA, Orozco M. Fast atomistic molecular dynamics simulations from essential dynamics samplings. J Chem Theory Comput. 2012;8(3):792–799.
   PubMed Web of Science ®Google Scholar