Open Access
Subscription or Fee Access
Role of Mitochondria in Cell Biology: A Brief Account
Abstract
Due to their pivotal role in energy production, mitochondria are conventionally mentioned to as the powerhouse of a cell. Today, mitochondria are documented as vital components of eukaryotic cell biology, regulating critical processes such as calcium signalling, cell metabolism, and cell death, among others. Nearly all eukaryotic cells encompass mitochondria, which are membrane-bound organelles that yield energy for cells. They are critical to maintaining life and preventing cell death. As a result of symbiotic ancestors, they carry mtDNA encoding 13 essential proteins for respiratory chain function as a residual genome. Mitochondria are divided into inter-membranous spaces, matrixes, and aqueous regions by inner and outer membranes. Cellular function and dysfunction are influenced by a wide range of mitochondrial processes including calcium signalling, cell growth, differentiation, cell cycle control, and cell death. Biogenesis, fission and fusion, and autophagy firmly regulate mitochondrial shape and positioning within cells, ensuring a comparatively constant mitochondrial population. A brief description of mitochondrial biology will be provided in this review, along with a snapshot of recent advances showing how mitochondria regulate other cellular processes.
References
Gray MW, Burger G, Lang BF. 1999. Mitochondrial evolution. Science 283, 1476–1481.
Lane N, Martin W. The energetics of genome complexity. Nature. 2010;467:929–934.
Anderson, A. J., Jackson, T. D., Stroud, D. A., & Stojanovski, D. (2019). Mitochondria-hubs for regulating cellular biochemistry: emerging concepts and networks. Open biology, 9(8), 190126.
Cogliati S, Enriquez JA, Scorrano L. 2016. Mitochondrial cristae: where beauty meets functionality. Trends Biochem. Sci. 41, 261–273.
Hoppins S, et al. 2011. A mitochondrial-focused genetic interaction map reveals a scaffold-like complex required for inner membrane organization in mitochondria. J. Cell Biol. 195, 323
Gödiker J, et al. 2018. QIL1-dependent assembly of MICOS complex–lethal mutation in C19ORF70 resulting in liver disease and severe neurological retardation. J. Hum. Genet. 63, 707–716.
Ding C, et al. 2015. Mitofilin and CHCHD6 physically interact with Sam50 to sustain cristae structure. Sci. Rep. 5, 16064
Darshi M, Mendiola VL, Mackey MR, Murphy AN, Koller A, Perkins GA, Ellisman MH, Taylor SS. 2011. ChChd3, an inner mitochondrial membrane protein, is essential for maintaining crista integrity and mitochondrial function. J. Biol. Chem. 286, 2918–2932.
Callegari S, et al. 2019. A MICOS-TIM22 association promotes carrier import into human mitochondria. J. Mol. Biol. 431, 2835–2851.
Tang J, et al. 2019. Sam50–Mic19–Mic60 axis determines mitochondrial cristae architecture by mediating mitochondrial outer and inner membrane contact. Cell Death Differ.
Nunnari J, Suomalainen A. Mitochondria: in sickness and in health. Cell. 2012;148:1145–1159.
Friedman, J. R., & Nunnari, J. (2014). Mitochondrial form and function. Nature, 505(7483), 335–343.
Ngo HB, Kaiser JT, Chan DC. The mitochondrial transcription and packaging factor Tfam imposes a U-turn on mitochondrial DNA. Nature Struct. Mol. Biol. 2011;18:1290–1296.
Rubio-Cosials A, et al. Human mitochondrial transcription factor A induces a U-turn structure in the light strand promoter. Nature Struct. Mol. Biol. 2011;18:1281–1289.
Ekstrand MI, et al. Mitochondrial transcription factor A regulates mtDNA copy number in mammals. Hum. Mol. Genet. 2004;13:935–944.
Shi Y, et al. Mammalian transcription factor A is a core component of the mitochondrial transcription machinery. Proc. Natl Acad. Sci. USA. 2012;109:16510–16515.
Bogenhagen DF. Mitochondrial DNA nucleoid structure. Biochim. Biophys. Acta. 2012;1819:914–920.
Copeland WC. Defects in mitochondrial DNA replication and human disease. Crit. Rev. Biochem. Mol. Biol. 2012;47:64–74.
Bogenhagen DF, Wang Y, Shen EL, Kobayashi R. Protein components of mitochondrial DNA nucleoids in higher eukaryotes. Mol. Cell. Proteomics. 2003;2:1205–1216.
He J, et al. Mitochondrial nucleoid interacting proteins support mitochondrial protein synthesis. Nucleic Acids Res. 2012;40:6109–6121.
Holt IJ, Reyes A. Human mitochondrial DNA replication. Cold Spring Harb. Perspect. Biol. 2012;4:a012971.
Brown TA, Tkachuk AN, Clayton DA. Native R-loops persist throughout the mouse mitochondrial DNA genome. J. Biol. Chem. 2008;283:36743–36751.
Brown TA, et al. Superresolution fluorescence imaging of mitochondrial nucleoids reveals their spatial range, limits, and membrane interaction. Mol. Cell. Biol. 2011;31:4994–5010.
Kukat C, et al. Super-resolution microscopy reveals that mammalian mitochondrial nucleoids have a uniform size and frequently contain a single copy of mtDNA. Proc. Natl Acad. Sci. USA. 2011;108:13534–13539.
Stojanovski D, Bragoszewski P, Chacinska A. 2012. The MIA pathway: a tight bond between protein transport and oxidative folding in mitochondria. Biochim. Biophys. Acta 1823, 1142–1150.
Frazier AE, Thorburn DR, Compton AG. 2017. Mitochondrial energy generation disorders: genes, mechanisms and clues to pathology. J. Biol. Chem. 294, 5386–5395.
Fillingame RH, Angevine CM, Dmitriev OY. 2003. Mechanics of coupling proton movements to c-ring rotation in ATP synthase. FEBS Lett. 555, 29–34.
Dizdaroglu M, Jaruga P. 2012. Mechanisms of free radical-induced damage to DNA. Free Radic. Res. 46, 382–419.
Niforou K, Cheimonidou C, Trougakos IP. 2014. Molecular chaperones and proteostasis regulation during redox imbalance. Redox Biol. 2, 323–332.
Letts JA, Sazanov LA. 2017. Clarifying the supercomplex: the higher-order organization of the mitochondrial electron transport chain. Nat. Struct. Mol. Biol. 24, 800–808.
Wang L. 2016. Mitochondrial purine and pyrimidine metabolism and beyond. Nucleosides Nucleotides Nucleic Acids 35, 578–594. ( 10.1080/15257770.2015.1125001)
Kastaniotis AJ, et al. 2017. Mitochondrial fatty acid synthesis, fatty acids and mitochondrial physiology. Biochim. Biophys. Acta Mol. Cell Biol. Lipids 1862, 39–48.
Ducker GS, Rabinowitz JD. 2017. One-carbon metabolism in health and disease. Cell Metab. 25, 27–42.
Grillo MA, Colombatto S. 2005. S-Adenosylmethionine and protein methylation. Amino Acids 28, 357–362.
Shimazu T, et al. 2013. Suppression of oxidative stress by beta-hydroxybutyrate, an endogenous histone deacetylase inhibitor. Science 339, 211–214.
Frezza C. 2017. Mitochondrial metabolites: undercover signalling molecules. Interface focus 7, 20160100
Thoreen CC, Chantranupong L, Keys HR, Wang T, Gray NS, Sabatini DM. 2012. A unifying model for mTORC1-mediated regulation of mRNA translation. Nature 485, 109–113.
Cunningham JT, Rodgers JT, Arlow DH, Vazquez F, Mootha VK, Puigserver P. 2007. mTOR controls mitochondrial oxidative function through a YY1–PGC-1α transcriptional complex. Nature 450, 736–740.
Morita M, et al. 2013. mTORC1 controls mitochondrial activity and biogenesis through 4E-BP-dependent translational regulation. Cell Metab. 18, 698–711.
Feng Z, Zhang H, Levine AJ, Jin S. 2005. The coordinate regulation of the p53 and mTOR pathways in cells. Proc. Natl Acad. Sci. USA 102, 8204–8209.
Horton LE, Bushell M, Barth-Baus D, Tilleray VJ, Clemens MJ, Hensold JO. 2002. p53 activation results in rapid dephosphorylation of the eIF4E-binding protein 4E-BP1, inhibition of ribosomal protein S6 kinase and inhibition of translation initiation. Oncogene 21, 5325–5334.
Matoba S, et al. 2006. p53 regulates mitochondrial respiration. Science 312, 1650–1653.
Kulawiec M, Ayyasamy V, Singh KK. 2009. p53 regulates mtDNA copy number and mitocheckpoint pathway. J. Carcinog. 8, 8
Achanta G, Sasaki R, Feng L, Carew JS, Lu W, Pelicano H, Keating MJ, Huang P. 2005. Novel role of p53 in maintaining mitochondrial genetic stability through interaction with DNA Pol gamma. EMBO J. 24, 3482–3492.
Hu W, Zhang C, Wu R, Sun Y, Levine A, Feng Z. 2010. Glutaminase 2, a novel p53 target gene regulating energy metabolism and antioxidant function. Proc. Natl Acad. Sci. USA 107, 7455–7460.
Bensaad K, Tsuruta A, Selak MA, Vidal MN, Nakano K, Bartrons R, Gottlieb E, Vousden KH. 2006. TIGAR, a p53-inducible regulator of glycolysis and apoptosis. Cell 126, 107–120.
Schwartzenberg-Bar-Yoseph F, Armoni M, Karnieli E. 2004. The tumor suppressor p53 down-regulates glucose transporters GLUT1 and GLUT4 gene expression. Cancer Res. 64, 2627
Elstrom RL, et al. 2004. Akt stimulates aerobic glycolysis in cancer cells. Cancer Res. 64, 3892–3899.
Kondoh H, et al. 2005. Glycolytic enzymes can modulate cellular life span. Cancer Res. 65, 177–185.
Brand, M. D., Orr, A. L., Perevoshchikova, I. V., & Quinlan, C. L. (2013). The role of mitochondrial function and cellular bioenergetics in ageing and disease. The British journal of dermatology, 169 Suppl 2(0 2), 1–8.
Tan W, Colombini M. 2007. VDAC closure increases calcium ion flux. Biochim. Biophys. Acta 1768, 2510–2515.
Scorziello A, et al. 2013. NCX3 regulates mitochondrial Ca2+ handling through the AKAP121-anchored signaling complex and prevents hypoxia-induced neuronal death. J. Cell Sci. 126, 5566–5577.
Patron M, et al. 2014. MICU1 and MICU2 finely tune the mitochondrial Ca2+ uniporter by exerting opposite effects on MCU activity. Mol. Cell 53, 726–737.
Petrungaro C, Zimmermann KM, Kuttner V, Fischer M, Dengjel J, Bogeski I, Riemer J. 2015. The Ca2+-dependent release of the Mia40-induced MICU1-MICU2 dimer from MCU regulates mitochondrial Ca2+ uptake. Cell Metab. 22, 721–733.
Giorgi C, Danese A, Missiroli S, Patergnani S, Pinton P. 2018. Calcium dynamics as a machine for decoding signals. Trends Cell Biol. 28, 258–273.
Giorgi C, Marchi S, Pinton P. 2018. The machineries, regulation and cellular functions of mitochondrial calcium. Nat. Rev. Mol. Cell Biol. 19, 713–730.
Kang JS, Tian JH, Pan PY, Zald P, Li C, Deng C, Sheng Z-H. 2008. Docking of axonal mitochondria by syntaphilin controls their mobility and affects short-term facilitation. Cell 132, 137–148.
David G, Barrett EF. 2003. Mitochondrial Ca2+ uptake prevents desynchronization of quantal release and minimizes depletion during repetitive stimulation of mouse motor nerve terminals. J. Physiol. 548, 425–438.
Rizzuto R, Pinton P, Carrington W, Fay FS, Fogarty KE, Lifshitz LM, Tuft RA, Pozzan T. 1998. Close contacts with the endoplasmic reticulum as determinants of mitochondrial Ca2+ responses. Science 280, 1763–1766. ( 10.1126/science.280.5370.1763)
Paillusson S, Gomez-Suaga P, Stoica R, Little D, Gissen P, Devine MJ, Noble W, Hanger DP, Miller CCJ. 2017. α-Synuclein binds to the ER-mitochondria tethering protein VAPB to disrupt Ca2+ homeostasis and mitochondrial ATP production. Acta Neuropathol. 134, 129–149.
Wiederkehr A, et al. 2011. Mitochondrial matrix calcium is an activating signal for hormone secretion. Cell Metab. 13, 601–611.
Antony AN, et al. 2016. MICU1 regulation of mitochondrial Ca2+ uptake dictates survival and tissue regeneration. Nat. Commun. 7, 10955 ( 10.1038/ncomms10955)
Cheng J, Liao Y, Zhou L, Peng S, Chen H, Yuan Z. 2016. Amplified RLR signaling activation through an interferon-stimulated gene-endoplasmic reticulum stress-mitochondrial calcium uniporter protein loop. Sci. Rep. 6, 20158
Horner SM, Liu HM, Park HS, Briley J, Gale M Jr. 2011. Mitochondrial-associated endoplasmic reticulum membranes (MAM) form innate immune synapses and are targeted by hepatitis C virus. Proc. Natl Acad. Sci. USA 108, 14 590–14 595.
West AP, Shadel GS, Ghosh S. 2011. Mitochondria in innate immune responses. Nat. Rev. Immunol. 11, 389–402.
Tang ED, Wang C-Y. 2009. MAVS self-association mediates antiviral innate immune signaling. J. Virol. 83, 3420–3428.
Liu XY, Wei B, Shi HX, Shan YF, Wang C. 2010. Tom70 mediates activation of interferon regulatory factor 3 on mitochondria. Cell Res. 20, 994–1011.
Tattoli I, Carneiro LA, Jehanno M, Magalhaes JG, Shu Y, Philpott DJ, Arnoult D, Girardin SE. 2008. NLRX1 is a mitochondrial NOD-like receptor that amplifies NF-κB and JNK pathways by inducing reactive oxygen species production. EMBO Rep. 9, 293–300.
Arnoult D, Soares F, Tattoli I, Castanier C, Philpott DJ, Girardin SE. 2009. An N-terminal addressing sequence targets NLRX1 to the mitochondrial matrix. J. Cell Sci. 122, 3161–3168.
Fielden LF, Kang Y, Newton HJ, Stojanovski D. 2017. Targeting mitochondria: how intravacuolar bacterial pathogens manipulate mitochondria. Cell Tissue Res. 367, 141–154.
Allam R, et al. 2014. Mitochondrial apoptosis is dispensable for NLRP3 inflammasome activation but non-apoptotic caspase-8 is required for inflammasome priming. EMBO Rep. 15, 982–990.
Nakahira K, et al. 2011. Autophagy proteins regulate innate immune responses by inhibiting the release of mitochondrial DNA mediated by the NALP3 inflammasome. Nat. Immunol. 12, 222–230.
Sanin DE, et al. 2018. Mitochondrial membrane potential regulates nuclear gene expression in macrophages exposed to prostaglandin E2. Immunity 49, 1021–1033.
De Simone R, Ajmone-Cat MA, Pandolfi M, Bernardo A, De Nuccio C, Minghetti L, Visentin S. et al. 2015. The mitochondrial uncoupling protein-2 is a master regulator of both M1 and M2 microglial responses. J. Neurochem. 135, 147–156.
Jha AK, et al. 2015. Network integration of parallel metabolic and transcriptional data reveals metabolic modules that regulate macrophage polarization. Immunity 42, 419–430.
Angajala A, Lim S, Phillips JB, Kim J-H, Yates C, You Z, Tan M. 2018. Diverse roles of mitochondria in immune responses: novel insights into immuno-metabolism. Front. Immunol. 9, 1605
Arsenijevic D, et al. 2000. Disruption of the uncoupling protein-2 gene in mice reveals a role in immunity and reactive oxygen species production. Nat. Genet. 26, 435–439.
Pearce EL, et al. 2009. Enhancing CD8 T-cell memory by modulating fatty acid metabolism. Nature 460, 103–107.
Chao T, Wang H, Ho P-C. 2017. Mitochondrial control and guidance of cellular activities of T cells. Front. Immunol. 8, 473
Buck MD, et al. 2016. Mitochondrial dynamics controls T cell fate through metabolic programming. Cell 166, 63–76.
yrakis PA, et al. 2016. S-2-hydroxyglutarate regulates CD8+ T-lymphocyte fate. Nature 540, 236–241.
van der Windt Gerritje JW, et al. 2012. Mitochondrial respiratory capacity is a critical regulator of CD8+ T cell memory development. Immunity 36, 68–78.
Lee S, Kim S, Sun X, Lee J-H, Cho H. 2007. Cell cycle-dependent mitochondrial biogenesis and dynamics in mammalian cells. Biochem. Biophys. Res. Commun. 357, 111–117.
Mitra K, Wunder C, Roysam B, Lin G, Lippincott-Schwartz J. 2009. A hyperfused mitochondrial state achieved at G1–S regulates cyclin E buildup and entry into S phase. Proc. Natl Acad. Sci. USA 106, 11 960–11 965.
Gregg T, Sdao SM, Dhillon RS, Rensvold JW, Lewandowski SL, Pagliarini DJ, Denu JM, Merrins MJ. 2019. Obesity-dependent CDK1 signaling stimulates mitochondrial respiration at complex I in pancreatic beta-cells. J. Biol. Chem. 294, 4656–4666.
Harbauer AB, et al. 2014. Cell cycle-dependent regulation of mitochondrial preprotein translocase. Science 346, 1109–1113.
Lee S, Kim S, Sun X, Lee J-H, Cho H. 2007. Cell cycle-dependent mitochondrial biogenesis and dynamics in mammalian cells. Biochem. Biophys. Res. Commun. 357, 111–117.
Martínez-Diez M, Santamaría G, Ortega ÁD, Cuezva JM. 2006. Biogenesis and dynamics of mitochondria during the cell cycle: significance of 3′UTRs. PLoS ONE 1, e107
Chen Y-C, Chang M-Y, Shiau A-L, Yo Y-T, Wu C-L. 2007. Mitochondrial ribosomal protein S36 delays cell cycle progression in association with p53 modification and p21WAF1/CIP1 expression. J. Cell. Biochem. 100, 981–990.
Shiraki N, et al. 2014. Methionine metabolism regulates maintenance and differentiation of human pluripotent stem cells. Cell Metab. 19, 780–794.
Owusu-Ansah E, Yavari A, Mandal S, Banerjee U. 2008. Distinct mitochondrial retrograde signals control the G1-S cell cycle checkpoint. Nat. Genet. 40, 356–361.
Chen K-H, Dasgupta A, Ding J, Indig FE, Ghosh P, Longo DL. 2014. Role of mitofusin 2 (Mfn2) in controlling cellular proliferation. FASEB J. 28, 382–394.
Cho YM, Kwon S, Pak YK, Seol HW, Choi YM, Park DJ, Park KS, Lee HK. 2006. Dynamic changes in mitochondrial biogenesis and antioxidant enzymes during the spontaneous differentiation of human embryonic stem cells. Biochem. Biophys. Res. Commun. 348, 1472–1478.
Takubo K, et al. 2013. Regulation of glycolysis by Pdk functions as a metabolic checkpoint for cell cycle quiescence in hematopoietic stem cells. Cell Stem Cell 12, 49–61.
Solari C, et al. 2018. Superoxide dismutase 1 expression is modulated by the core pluripotency transcription factors Oct4, Sox2 and Nanog in embryonic stem cells. Mech. Dev. 154, 116–121.
Kasahara A, Cipolat S, Chen Y, Dorn GW, Scorrano L. 2013. Mitochondrial fusion directs cardiomyocyte differentiation via calcineurin and Notch signaling. Science 342, 734–737.
Sin J, et al. 2015. Mitophagy is required for mitochondrial biogenesis and myogenic differentiation of C2C12 myoblasts. Autophagy 12, 369–380.
Son MJ, et al. 2015. Mitofusins deficiency elicits mitochondrial metabolic reprogramming to pluripotency. Cell Death Differ. 22, 1957
Son M-Y, Choi H, Han Y-M, Sook Cho Y. 2013. Unveiling the critical role of REX1 in the regulation of human stem cell pluripotency. Stem Cells 31, 2374–2387.
Kuwana T, Mackey MR, Perkins G, Ellisman MH, Latterich M, Schneiter R, Green DR, Newmeyer DD. 2002. Bid, Bax, and lipids cooperate to form supramolecular openings in the outer mitochondrial membrane. Cell 111, 331–342.
Du C, Fang M, Li Y, Li L, Wang X. 2000. Smac, a mitochondrial protein that promotes cytochrome c-dependent caspase activation by eliminating IAP inhibition. Cell 102, 33–42.
Verhagen AM, et al. 2002. HtrA2 promotes cell death through its serine protease activity and its ability to antagonize inhibitor of apoptosis proteins. J. Biol. Chem. 277, 445–454.
Sevrioukova IF. 2011. Apoptosis-inducing factor: structure, function, and redox regulation. Antioxid. Redox Signal. 14, 2545–2579.
van Loo G, et al. 2001. Endonuclease G: a mitochondrial protein released in apoptosis and involved in caspase-independent DNA degradation. Cell Death Differ. 8, 1136
Cheng EH-Y, Sheiko TV, Fisher JK, Craigen WJ, Korsmeyer SJ. 2003. VDAC2 inhibits BAK activation and mitochondrial apoptosis. Science 301, 513–517.
Lazarou M, et al. 2010. Inhibition of Bak activation by VDAC2 is dependent on the Bak transmembrane anchor. J. Biol. Chem. 285, 36 876–36 883.
Chin HS, et al. 2018. VDAC2 enables BAX to mediate apoptosis and limit tumor development. Nat. Commun. 9, 4976
Angelina VV, Natalie DM, Ji K, Tsirka Stella E, Holzmann S, Moll Ute M. 2012. p53 opens the mitochondrial permeability transition pore to trigger necrosis. Cell 149, 1536–1548.
Wang Z, Jiang H, Chen S, Du F, Wang X. 2012. The mitochondrial phosphatase PGAM5 functions at the convergence point of multiple necrotic death pathways. Cell 148, 228–243.
Wu C, Zhao W, Yu J, Li S, Lin L, Chen X. 2018. Induction of ferroptosis and mitochondrial dysfunction by oxidative stress in PC12 cells. Sci. Rep. 8, 574
Gao M, et al. 2019. Role of mitochondria in ferroptosis. Mol. Cell 73, 354–363.
Fatokun AA, Dawson VL, Dawson TM. 2014. Parthanatos: mitochondrial-linked mechanisms and therapeutic opportunities. Br. J. Pharmacol. 171, 2000–2016.
Zhao Q, Wang J, Levichkin IV, Stasinopoulos S, Ryan MT, Hoogenraad NJ. 2002. A mitochondrial specific stress response in mammalian cells. EMBO J. 21, 4411–4419.
Fiorese CJ, Schulz AM, Lin Y-F, Rosin N, Pellegrino MW, Haynes CM. 2016. The transcription factor ATF5 mediates a mammalian mitochondrial UPR. Curr. Biol. 26, 2037–2043.
Monaco SE, Angelastro JM, Szabolcs M, Greene LA. 2007. The transcription factor ATF5 is widely expressed in carcinomas, and interference with its function selectively kills neoplastic, but not nontransformed, breast cell lines. Int. J. Cancer 120, 1883–1890.
Nargund AM, Fiorese CJ, Pellegrino MW, Deng P, Haynes CM. 2015. Mitochondrial and nuclear accumulation of the transcription factor ATFS-1 promotes OXPHOS recovery during the UPR(mt). Mol. Cell 58, 123–133.
Zhou D, Palam LR, Jiang L, Narasimhan J, Staschke KA, Wek RC. 2008. Phosphorylation of eIF2 directs ATF5 translational control in response to diverse stress conditions. J. Biol. Chem. 283, 7064–7073.
Quirós PM, Prado MA, Zamboni N, D'Amico D, Williams RW, Finley D, Gygi SP, Auwerx J. 2017. Multi-omics analysis identifies ATF4 as a key regulator of the mitochondrial stress response in mammals. J. Cell Biol. 216, 2027–2045.
Harding HP, et al. 2003. An integrated stress response regulates amino acid metabolism and resistance to oxidative stress. Mol. Cell 11, 619–633.
Rainbolt TK, Atanassova N, Genereux JC, Wiseman RL. 2013. Stress-regulated translational attenuation adapts mitochondrial protein import through Tim17A degradation. Cell Metab. 18, 908–919.
Pakos-Zebrucka K, Koryga I, Mnich K, Ljujic M, Samali A, Gorman AM. 2016. The integrated stress response. EMBO Rep. 17, 1374–1395.
Okatsu K, Kimura M, Oka T, Tanaka K, Matsuda N. 2015. Unconventional PINK1 localization to the outer membrane of depolarized mitochondria drives Parkin recruitment. J. Cell Sci. 128, 964–978.
Jin SM, Lazarou M, Wang C, Kane LA, Narendra DP, Youle RJ. 2010. Mitochondrial membrane potential regulates PINK1 import and proteolytic destabilization by PARL. J. Cell Biol. 191, 933–942.
Lazarou M, Jin SM, Kane LA, Youle RJ. 2012. Role of PINK1 binding to the TOM complex and alternate intracellular membranes in recruitment and activation of the E3 ligase Parkin. Dev. Cell 22, 320–333.
Okatsu K, et al. 2012. PINK1 autophosphorylation upon membrane potential dissipation is essential for Parkin recruitment to damaged mitochondria. Nat. Commun. 3, 1016
Sarraf SA, et al. 2013. Landscape of the PARKIN-dependent ubiquitylome in response to mitochondrial depolarization. Nature 496, 372–376.
Ordureau A, et al. 2014. Quantitative proteomics reveal a feedforward mechanism for mitochondrial PARKIN translocation and ubiquitin chain synthesis. Mol. Cell 56, 360–375.
Refbacks
- There are currently no refbacks.