Lewis, M. R. & Lewis. W. H. Mitochondria (and other cytoplasmic structures) in tissue cultures. Am. J. Anat. 17, 339–401 (1915).
Spinelli, J. B. & Haigis, M. C. The multifaceted contributions of mitochondria to cellular metabolism. Nat. Cell Biol. 20, 745–754 (2018).
Google Scholar
Jornayvaz, F. R. & Shulman, G. I. Regulation of mitochondrial biogenesis. Essays Biochem. 47, 69–84 (2010).
Google Scholar
Schmitt, K. et al. Circadian control of DRP1 activity regulates mitochondrial dynamics and bioenergetics. Cell Metab. 27, 657–666 (2018).
Google Scholar
Kraus, F. & Ryan, M. T. The constriction and scission machineries involved in mitochondrial fission. J. Cell Sci. 130, 2953–2960 (2017).
Google Scholar
Youle, R. J. & van der Bliek, A. M. Mitochondrial fission, fusion, and stress. Science 337, 1062–1065 (2012).
Google Scholar
Giacomello, M., Pyakurel, A., Glytsou, C. & Scorrano, L. The cell biology of mitochondrial membrane dynamics. Nat. Rev. Mol. Cell Biol. 21, 204–224 (2020).
Google Scholar
Kuroiwa, T. et al. Structure, function and evolution of the mitochondrial division apparatus. Biochim. Biophys. Acta 1763, 510–521 (2006).
Google Scholar
Eme, L., Spang, A., Lombard, J., Stairs, C. W. & Ettema, T. J. G. Archaea and the origin of eukaryotes. Nat. Rev. Microbiol. 15, 711–723 (2017).
Google Scholar
Rowlett, V. W. & Margolin, W. The bacterial divisome: ready for its close-up. Phil. Trans. R. Soc. Lond. B 370, 20150028 (2015).
Haeusser, D. P. & Margolin, W. Splitsville: structural and functional insights into the dynamic bacterial Z ring. Nat. Rev. Microbiol. 14, 305–319 (2016).
Google Scholar
Osteryoung, K. W. & Nunnari, J. The division of endosymbiotic organelles. Science 302, 1698–1704 (2003).
Google Scholar
Nishida, K. et al. Triple immunofluorescent labeling of FtsZ, dynamin, and EF-Tu reveals a loose association between the inner and outer membrane mitochondrial division machinery in the red alga Cyanidioschyzon merolae. J. Histochem. Cytochem. 52, 843–849 (2004).
Google Scholar
Kamerkar, S. C., Kraus, F., Sharpe, A. J., Pucadyil, T. J. & Ryan, M. T. Dynamin-related protein 1 has membrane constricting and severing abilities sufficient for mitochondrial and peroxisomal fission. Nat. Commun. 9, 5239 (2018). This study demonstrates that DRP1 can sever membrane tubules and is independent of endocytic dynamins in mitochondrial fission.
Google Scholar
Smirnova, E., Griparic, L., Shurland, D. L. & van der Bliek, A. M. Dynamin-related protein Drp1 is required for mitochondrial division in mammalian cells. Mol. Biol. Cell 12, 2245–2256 (2001).
Google Scholar
Ishihara, N. et al. Mitochondrial fission factor Drp1 is essential for embryonic development and synapse formation in mice. Nat. Cell Biol. 11, 958–966 (2009).
Google Scholar
Wakabayashi, J. et al. The dynamin-related GTPase Drp1 is required for embryonic and brain development in mice. J. Cell Biol. 186, 805–816 (2009).
Google Scholar
Rosenbloom, A. B. et al. Optimized two-color super resolution imaging of Drp1 during mitochondrial fission with a slow-switching Dronpa variant. Proc. Natl Acad. Sci. USA 111, 13093–13098 (2014).
Google Scholar
Koch, A. et al. Dynamin-like protein 1 is involved in peroxisomal fission. J. Biol. Chem. 278, 8597–8605 (2003).
Google Scholar
Kalia, R. et al. Structural basis of mitochondrial receptor binding and constriction by DRP1. Nature 558, 401–405 (2018). Structural insights from a complex of DRP1 with its adaptor suggest a mechanism for adaptor disengagement from DRP1 upon GTP hydrolysis.
Google Scholar
Reubold, T. F. et al. Crystal structure of the dynamin tetramer. Nature 525, 404–408 (2015).
Google Scholar
Ford, M. G., Jenni, S. & Nunnari, J. The crystal structure of dynamin. Nature 477, 561–566 (2011).
Google Scholar
Faelber, K. et al. Crystal structure of nucleotide-free dynamin. Nature 477, 556–560 (2011).
Google Scholar
Bohuszewicz, O. & Low, H. H. Structure of a mitochondrial fission dynamin in the closed conformation. Nat. Struct. Mol. Biol. 25, 722–731 (2018).
Google Scholar
Kong, L. et al. Cryo-EM of the dynamin polymer assembled on lipid membrane. Nature 560, 258–262 (2018).
Google Scholar
Gao, S. et al. Structure of myxovirus resistance protein a reveals intra- and intermolecular domain interactions required for the antiviral function. Immunity 35, 514–525 (2011).
Google Scholar
Adachi, Y. et al. Coincident phosphatidic acid interaction restrains Drp1 in mitochondrial division. Mol. Cell 63, 1034–1043 (2016).
Google Scholar
Bustillo-Zabalbeitia, I. et al. Specific interaction with cardiolipin triggers functional activation of dynamin-related protein 1. PLoS ONE 9, e102738 (2014).
Google Scholar
Francy, C. A., Clinton, R. W., Fröhlich, C., Murphy, C. & Mears, J. A. Cryo-EM studies of Drp1 reveal cardiolipin interactions that activate the helical oligomer. Sci. Rep. 7, 10744 (2017).
Google Scholar
Stepanyants, N. et al. Cardiolipin’s propensity for phase transition and its reorganization by dynamin-related protein 1 form a basis for mitochondrial membrane fission. Mol. Biol. Cell 26, 3104–3116 (2015).
Google Scholar
Strack, S. & Cribbs, J. T. Allosteric modulation of Drp1 mechanoenzyme assembly and mitochondrial fission by the variable domain. J. Biol. Chem. 287, 10990–11001 (2012).
Google Scholar
Clinton, R. W., Francy, C. A., Ramachandran, R., Qi, X. & Mears, J. A. Dynamin-related protein 1 oligomerization in solution impairs functional interactions with membrane-anchored mitochondrial fission factor. J. Biol. Chem. 291, 478–492 (2016).
Google Scholar
Lu, B. et al. Steric interference from intrinsically disordered regions controls dynamin-related protein 1 self-assembly during mitochondrial fission. Sci. Rep. 8, 10879 (2018).
Google Scholar
Koirala, S. et al. Interchangeable adaptors regulate mitochondrial dynamin assembly for membrane scission. Proc. Natl Acad. Sci. USA 110, E1342–E1351 (2013). A systematic analysis of the independent contribution of adaptors to mitochondrial division.
Google Scholar
Lackner, L. L., Horner, J. S. & Nunnari, J. Mechanistic analysis of a dynamin effector. Science 325, 874–877 (2009).
Google Scholar
Osellame, L. D. et al. Cooperative and independent roles of the Drp1 adaptors Mff, MiD49 and MiD51 in mitochondrial fission. J. Cell Sci. 129, 2170–2181 (2016).
Google Scholar
Otera, H. et al. Mff is an essential factor for mitochondrial recruitment of Drp1 during mitochondrial fission in mammalian cells. J. Cell Biol. 191, 1141–1158 (2010). This paper establishes that MFF recruits DRP1 for fission, whereas FIS1 is dispensable.
Google Scholar
Arimura, S. I. Fission and fusion of plant mitochondria, and genome maintenance. Plant Physiol. 176, 152–161 (2018).
Google Scholar
Melatti, C. et al. A unique dynamin-related protein is essential for mitochondrial fission in Toxoplasma gondii. PLoS Pathog. 15, e1007512 (2019).
Google Scholar
Xian, H., Yang, Q., Xiao, L., Shen, H. M. & Liou, Y. C. STX17 dynamically regulated by Fis1 induces mitophagy via hierarchical macroautophagic mechanism. Nat. Commun. 10, 2059 (2019).
Google Scholar
Shen, Q. et al. Mutations in Fis1 disrupt orderly disposal of defective mitochondria. Mol. Biol. Cell 25, 145–159 (2014).
Google Scholar
Costello, J. L. et al. Predicting the targeting of tail-anchored proteins to subcellular compartments in mammalian cells. J. Cell Sci. 130, 1675–1687 (2017).
Google Scholar
Gandre-Babbe, S. & van der Bliek, A. M. The novel tail-anchored membrane protein Mff controls mitochondrial and peroxisomal fission in mammalian cells. Mol. Biol. Cell 19, 2402–2412 (2008). The discovery of MFF is reported, and the fact that loss of MFF phenocopies loss of DRP1 is demonstrated.
Google Scholar
Otera, H., Miyata, N., Kuge, O. & Mihara, K. Drp1-dependent mitochondrial fission via MiD49/51 is essential for apoptotic cristae remodeling. J. Cell Biol. 212, 531–544 (2016).
Google Scholar
Losón, O. C. et al. The mitochondrial fission receptor MiD51 requires ADP as a cofactor. Structure 22, 367–377 (2014).
Google Scholar
Losón, O. C. et al. Crystal structure and functional analysis of MiD49, a receptor for the mitochondrial fission protein Drp1. Protein Sci. 24, 386–394 (2015).
Google Scholar
Losón, O. C., Song, Z., Chen, H. & Chan, D. C. Fis1, Mff, MiD49, and MiD51 mediate Drp1 recruitment in mitochondrial fission. Mol. Biol. Cell 24, 659–667 (2013).
Google Scholar
Palmer, C. S. et al. MiD49 and MiD51, new components of the mitochondrial fission machinery. EMBO Rep. 12, 565–573 (2011). This study reports the discovery of MiD proteins as adaptors for DRP1.
Google Scholar
Richter, V. et al. Structural and functional analysis of MiD51, a dynamin receptor required for mitochondrial fission. J. Cell Biol. 204, 477–486 (2014).
Google Scholar
Ma, J. et al. New interfaces on MiD51 for Drp1 recruitment and regulation. PLoS ONE 14, e0211459 (2019).
Google Scholar
Liu, R. & Chan, D. C. The mitochondrial fission receptor Mff selectively recruits oligomerized Drp1. Mol. Biol. Cell 26, 4466–4477 (2015).
Google Scholar
Zhang, Z., Liu, L., Wu, S. & Xing, D. Drp1, Mff, Fis1, and MiD51 are coordinated to mediate mitochondrial fission during UV irradiation-induced apoptosis. FASEB J. 30, 466–476 (2016).
Google Scholar
Palmer, C. S. et al. Adaptor proteins MiD49 and MiD51 can act independently of Mff and Fis1 in Drp1 recruitment and are specific for mitochondrial fission. J. Biol. Chem. 288, 27584–27593 (2013).
Google Scholar
Elgass, K. D., Smith, E. A., LeGros, M. A., Larabell, C. A. & Ryan, M. T. Analysis of ER–mitochondria contacts using correlative fluorescence microscopy and soft X-ray tomography of mammalian cells. J. Cell Sci. 128, 2795–2804 (2015).
Google Scholar
Friedman, J. R. et al. ER tubules mark sites of mitochondrial division. Science 334, 358–362 (2011). The authors report the role of the ER in inducing mitochondrial constriction sites for fission.
Google Scholar
Helle, S. C. J. et al. Mechanical force induces mitochondrial fission. eLife 6, e30292 (2017).
Google Scholar
Itoh, K. et al. A brain-enriched Drp1 isoform associates with lysosomes, late endosomes, and the plasma membrane. J. Biol. Chem. 293, 11809–11822 (2018).
Google Scholar
Ford, M. G. J. & Chappie, J. S. The structural biology of the dynamin-related proteins: new insights into a diverse, multitalented family. Traffic 20, 717–740 (2019).
Google Scholar
Macdonald, P. J. et al. Distinct splice variants of dynamin-related protein 1 differentially utilize mitochondrial fission factor as an effector of cooperative GTPase activity. J. Biol. Chem. 291, 493–507 (2016).
Google Scholar
Chang, C. R. & Blackstone, C. Dynamic regulation of mitochondrial fission through modification of the dynamin-related protein Drp1. Ann. NY Acad. Sci. 1201, 34–39 (2010).
Google Scholar
Otera, H., Ishihara, N. & Mihara, K. New insights into the function and regulation of mitochondrial fission. Biochim. Biophys. Acta 1833, 1256–1268 (2013).
Google Scholar
Cribbs, J. T. & Strack, S. Reversible phosphorylation of Drp1 by cyclic AMP-dependent protein kinase and calcineurin regulates mitochondrial fission and cell death. EMBO Rep. 8, 939–944 (2007).
Google Scholar
Cereghetti, G. M. et al. Dephosphorylation by calcineurin regulates translocation of Drp1 to mitochondria. Proc. Natl Acad. Sci. USA 105, 15803–15808 (2008).
Google Scholar
Mishra, P. & Chan, D. C. Metabolic regulation of mitochondrial dynamics. J. Cell Biol. 212, 379–387 (2016).
Google Scholar
Yu, B. et al. Mitochondrial phosphatase PGAM5 modulates cellular senescence by regulating mitochondrial dynamics. Nat. Commun. 11, 2549 (2020).
Google Scholar
Cherok, E. et al. Novel regulatory roles of Mff and Drp1 in E3 ubiquitin ligase MARCH5-dependent degradation of MiD49 and Mcl1 and control of mitochondrial dynamics. Mol. Biol. Cell 28, 396–410 (2017).
Google Scholar
Xu, S. et al. Mitochondrial E3 ubiquitin ligase MARCH5 controls mitochondrial fission and cell sensitivity to stress-induced apoptosis through regulation of MiD49 protein. Mol. Biol. Cell 27, 349–359 (2016).
Google Scholar
Toyama, E. Q. et al. Metabolism. AMP-activated protein kinase mediates mitochondrial fission in response to energy stress. Science 351, 275–281 (2016). A kinase-controlled signalling axis that links metabolism to mitochondrial division is delineated.
Google Scholar
de Brito, O. M. & Scorrano, L. An intimate liaison: spatial organization of the endoplasmic reticulum–mitochondria relationship. EMBO J. 29, 2715–2723 (2010).
Google Scholar
Giacomello, M. & Pellegrini, L. The coming of age of the mitochondria–ER contact: a matter of thickness. Cell Death Differ. 23, 1417–1427 (2016).
Google Scholar
Vance, J. E. MAM (mitochondria-associated membranes) in mammalian cells: lipids and beyond. Biochim. Biophys. Acta 1841, 595–609 (2014).
Google Scholar
Phillips, M. J. & Voeltz, G. K. Structure and function of ER membrane contact sites with other organelles. Nat. Rev. Mol. Cell Biol. 17, 69–82 (2016).
Google Scholar
Li, S. et al. Transient assembly of F-actin on the outer mitochondrial membrane contributes to mitochondrial fission. J. Cell Biol. 208, 109–123 (2015).
Google Scholar
Moore, A. S., Wong, Y. C., Simpson, C. L. & Holzbaur, E. L. Dynamic actin cycling through mitochondrial subpopulations locally regulates the fission–fusion balance within mitochondrial networks. Nat. Commun. 7, 12886 (2016).
Google Scholar
Manor, U. et al. A mitochondria-anchored isoform of the actin–nucleating spire protein regulates mitochondrial division. eLife 4, (2015).
Korobova, F., Ramabhadran, V. & Higgs, H. N. An actin-dependent step in mitochondrial fission mediated by the ER-associated formin INF2. Science 339, 464–467 (2013). This study links actin dynamics, the ER and IFN2 to mitochondrial division.
Google Scholar
Chakrabarti, R. et al. INF2-mediated actin polymerization at the ER stimulates mitochondrial calcium uptake, inner membrane constriction, and division. J. Cell Biol. 217, 251–268 (2018).
Google Scholar
Yang, C. & Svitkina, T. M. Ultrastructure and dynamics of the actin–myosin II cytoskeleton during mitochondrial fission. Nat. Cell Biol. 21, 603–613 (2019).
Google Scholar
Korobova, F., Gauvin, T. J. & Higgs, H. N. A role for myosin II in mammalian mitochondrial fission. Curr. Biol. 24, 409–414 (2014).
Google Scholar
Hatch, A. L., Ji, W. K., Merrill, R. A., Strack, S. & Higgs, H. N. Actin filaments as dynamic reservoirs for Drp1 recruitment. Mol. Biol. Cell 27, 3109–3121 (2016).
Google Scholar
Wong, Y. C., Ysselstein, D. & Krainc, D. Mitochondria–lysosome contacts regulate mitochondrial fission via RAB7 GTP hydrolysis. Nature 554, 382–386 (2018). Lysosome–mitochondria contacts are shown to influence mitochondrial division.
Google Scholar
Nagashima, S. et al. Golgi-derived PI(4)P-containing vesicles drive late steps of mitochondrial division. Science 367, 1366–1371 (2020).
Google Scholar
Ackema, K. B. et al. The small GTPase Arf1 modulates mitochondrial morphology and function. EMBO J. 33, 2659–2675 (2014).
Google Scholar
Lewis, S. C., Uchiyama, L. F. & Nunnari, J. ER–mitochondria contacts couple mtDNA synthesis with mitochondrial division in human cells. Science 353, aaf5549 (2016). These results provide insights into the coordination between mitochondrial DNA replication and division.
Google Scholar
Stephan, T., Roesch, A., Riedel, D. & Jakobs, S. Live-cell STED nanoscopy of mitochondrial cristae. Sci. Rep. 9, 12419 (2019).
Google Scholar
Ishihara, N., Fujita, Y., Oka, T. & Mihara, K. Regulation of mitochondrial morphology through proteolytic cleavage of OPA1. EMBO J. 25, 2966–2977 (2006).
Google Scholar
Delettre, C. et al. Nuclear gene OPA1, encoding a mitochondrial dynamin-related protein, is mutated in dominant optic atrophy. Nat. Genet. 26, 207–210 (2000).
Google Scholar
Anand, R. et al. The i-AAA protease YME1L and OMA1 cleave OPA1 to balance mitochondrial fusion and fission. J. Cell Biol. 204, 919–929 (2014).
Google Scholar
Faelber, K. et al. Structure and assembly of the mitochondrial membrane remodelling GTPase Mgm1. Nature 571, 429–433 (2019).
Google Scholar
Zhang, D. et al. Cryo-EM structures of S-OPA1 reveal its interactions with membrane and changes upon nucleotide binding. eLife 9, e50294 (2020).
Google Scholar
Cho, B. et al. Constriction of the mitochondrial inner compartment is a priming event for mitochondrial division. Nat. Commun. 8, 15754 (2017).
Google Scholar
Fox, C. A., Ellison, P., Ikon, N. & Ryan, R. O. Calcium-induced transformation of cardiolipin nanodisks. Biochim. Biophys. Acta Biomembr. 1861, 1030–1036 (2019).
Google Scholar
Basu, K. et al. Molecular mechanism of DRP1 assembly studied in vitro by cryo-electron microscopy. PLoS ONE 12, e0179397 (2017).
Google Scholar
Ingerman, E. et al. Dnm1 forms spirals that are structurally tailored to fit mitochondria. J. Cell Biol. 170, 1021–1027 (2005).
Google Scholar
Chappie, J. S., Acharya, S., Leonard, M., Schmid, S. L. & Dyda, F. G domain dimerization controls dynamin’s assembly-stimulated GTPase activity. Nature 465, 435–440 (2010).
Google Scholar
Antonny, B. et al. Membrane fission by dynamin: what we know and what we need to know. EMBO J. 35, 2270–2284 (2016).
Google Scholar
Dar, S., Kamerkar, S. C. & Pucadyil, T. J. A high-throughput platform for real-time analysis of membrane fission reactions reveals dynamin function. Nat. Cell Biol. 17, 1588–1596 (2015).
Google Scholar
Dar, S., Kamerkar, S. C. & Pucadyil, T. J. Use of the supported membrane tube assay system for real-time analysis of membrane fission reactions. Nat. Protoc. 12, 390–400 (2017).
Google Scholar
Ferguson, S. M. et al. Coordinated actions of actin and BAR proteins upstream of dynamin at endocytic clathrin-coated pits. Dev. Cell 17, 811–822 (2009).
Google Scholar
Purkanti, R. & Thattai, M. Ancient dynamin segments capture early stages of host-mitochondrial integration. Proc. Natl Acad. Sci. USA 112, 2800–2805 (2015).
Google Scholar
Lee, J. E., Westrate, L. M., Wu, H., Page, C. & Voeltz, G. K. Multiple dynamin family members collaborate to drive mitochondrial division. Nature 540, 139–143 (2016).
Google Scholar
Fonseca, T. B., Sánchez-Guerrero, Á., Milosevic, I. & Raimundo, N. Mitochondrial fission requires DRP1 but not dynamins. Nature 570, E34–E42 (2019). DRP1, and not the endocytic dynamins, is shown to be necessary for mitochondrial fission.
Google Scholar
Favaro, G. et al. DRP1-mediated mitochondrial shape controls calcium homeostasis and muscle mass. Nat. Commun. 10, 2576 (2019).
Google Scholar
Hennings, T. G. et al. In vivo deletion of β-cell Drp1 impairs insulin secretion without affecting islet oxygen consumption. Endocrinology 159, 3245–3256 (2018).
Google Scholar
Simula, L. et al. Drp1 controls effective T cell immune-surveillance by regulating T cell migration, proliferation, and cMyc-dependent metabolic reprogramming. Cell Rep. 25, 3059–3073 (2018).
Google Scholar
Sesaki, H., Southard, S. M., Yaffe, M. P. & Jensen, R. E. Mgm1p, a dynamin-related GTPase, is essential for fusion of the mitochondrial outer membrane. Mol. Biol. Cell 14, 2342–2356 (2003).
Google Scholar
Chen, L. & Knowlton, A. A. Mitochondrial dynamics in heart failure. Congest. Heart Fail. 17, 257–261 (2011).
Google Scholar
Yamada, T. et al. Mitochondrial stasis reveals p62-mediated ubiquitination in Parkin-independent mitophagy and mitigates nonalcoholic fatty liver disease. Cell Metab. 28, 588–604 (2018).
Google Scholar
Verrigni, D. et al. Clinical-genetic features and peculiar muscle histopathology in infantile DNM1L-related mitochondrial epileptic encephalopathy. Hum. Mutat. 40, 601–618 (2019).
Google Scholar
Waterham, H. R. et al. A lethal defect of mitochondrial and peroxisomal fission. N. Engl. J. Med. 356, 1736–1741 (2007).
Google Scholar
Rahman, S. Mitochondrial disease and epilepsy. Dev. Med. Child Neurol. 54, 397–406 (2012).
Koch, J. et al. Disturbed mitochondrial and peroxisomal dynamics due to loss of MFF causes Leigh-like encephalopathy, optic atrophy and peripheral neuropathy. J. Med. Genet. 53, 270–278 (2016).
Google Scholar
Bartsakoulia, M. et al. A novel mechanism causing imbalance of mitochondrial fusion and fission in human myopathies. Hum. Mol. Genet. 27, 1186–1195 (2018).
Google Scholar
Twig, G. et al. Fission and selective fusion govern mitochondrial segregation and elimination by autophagy. EMBO J. 27, 433–446 (2008). Detailed microscopic observations reveal the importance of fission as a surveillance measure for mitochondrial quality control.
Google Scholar
Abrisch, R. G., Gumbin, S. C., Wisniewski, B. T., Lackner, L. L. & Voeltz, G. K. Fission and fusion machineries converge at ER contact sites to regulate mitochondrial morphology. J. Cell Biol. 219, e201911122 (2020). A role for the ER in regulating both mitochondrial fission and fusion machineries is established.
Google Scholar
Nguyen, T. N., Padman, B. S. & Lazarou, M. Deciphering the molecular signals of PINK1/Parkin mitophagy. Trends Cell Biol. 26, 733–744 (2016).
Google Scholar
Dikic, I. & Elazar, Z. Mechanism and medical implications of mammalian autophagy. Nat. Rev. Mol. Cell Biol. 19, 349–364 (2018).
Google Scholar
Gomes, L. C. & Scorrano, L. Mitochondrial morphology in mitophagy and macroautophagy. Biochim. Biophys. Acta 1833, 205–212 (2013).
Google Scholar
Lieber, T., Jeedigunta, S. P., Palozzi, J. M., Lehmann, R. & Hurd, T. R. Mitochondrial fragmentation drives selective removal of deleterious mtDNA in the germline. Nature 570, 380–384 (2019).
Google Scholar
Rana, A. et al. Promoting Drp1-mediated mitochondrial fission in midlife prolongs healthy lifespan of Drosophila melanogaster. Nat. Commun. 8, 448 (2017).
Google Scholar
Burman, J. L. et al. Mitochondrial fission facilitates the selective mitophagy of protein aggregates. J. Cell Biol. 216, 3231–3247 (2017). This study supports the role of DRP1 and division in segregating mitochondrial fragments away from the larger population for selective, rather than bulk, turnover.
Google Scholar
Bernard, G. et al. Mitochondrial bioenergetics and structural network organization. J. Cell Sci. 120, 838–848 (2007).
Pfluger, P. T. et al. Calcineurin links mitochondrial elongation with energy metabolism. Cell Metab. 22, 838–850 (2015).
Google Scholar
Kim, Y. M. et al. Redox regulation of mitochondrial fission protein Drp1 by protein disulfide isomerase limits endothelial senescence. Cell Rep. 23, 3565–3578 (2018).
Google Scholar
Chen, Z. et al. Global phosphoproteomic analysis reveals ARMC10 as an AMPK substrate that regulates mitochondrial dynamics. Nat. Commun. 10, 104 (2019).
Google Scholar
Herzig, S. & Shaw, R. J. AMPK: guardian of metabolism and mitochondrial homeostasis. Nat. Rev. Mol. Cell Biol. 19, 121–135 (2018).
Google Scholar
Morita, M. et al. mTOR controls mitochondrial dynamics and cell survival via MTFP1. Mol. Cell 67, 922–935 (2017).
Google Scholar
Hammerschmidt, P. et al. CerS6-derived sphingolipids interact with Mff and promote mitochondrial fragmentation in obesity. Cell 177, 1536–1552 (2019).
Google Scholar
Wang, L. et al. Disruption of mitochondrial fission in the liver protects mice from diet-induced obesity and metabolic deterioration. Diabetologia 58, 2371–2380 (2015).
Google Scholar
Buck, M. D. et al. Mitochondrial dynamics controls T cell fate through metabolic programming. Cell 166, 63–76 (2016).
Google Scholar
Prieto, J. et al. Early ERK1/2 activation promotes DRP1-dependent mitochondrial fission necessary for cell reprogramming. Nat. Commun. 7, 11124 (2016).
Google Scholar
Serasinghe, M. N. et al. Mitochondrial division is requisite to RAS-induced transformation and targeted by oncogenic MAPK pathway inhibitors. Mol. Cell 57, 521–536 (2015).
Google Scholar
Kashatus, J. A. et al. Erk2 phosphorylation of Drp1 promotes mitochondrial fission and MAPK-driven tumor growth. Mol. Cell 57, 537–551 (2015).
Google Scholar
Nagdas, S. et al. Drp1 promotes KRas-driven metabolic changes to drive pancreatic tumor growth. Cell Rep. 28, 1845–1859 (2019).
Google Scholar
Xie, Q. et al. Mitochondrial control by DRP1 in brain tumor initiating cells. Nat. Neurosci. 18, 501–510 (2015).
Google Scholar
Sheng, Z. H. The interplay of axonal energy homeostasis and mitochondrial trafficking and anchoring. Trends Cell Biol. 27, 403–416 (2017).
Google Scholar
Csordás, G. et al. Imaging interorganelle contacts and local calcium dynamics at the ER-mitochondrial interface. Mol. Cell 39, 121–132 (2010).
Google Scholar
MacAskill, A. F. & Kittler, J. T. Control of mitochondrial transport and localization in neurons. Trends Cell Biol. 20, 102–112 (2010).
Google Scholar
Chang, D. T., Honick, A. S. & Reynolds, I. J. Mitochondrial trafficking to synapses in cultured primary cortical neurons. J. Neurosci. 26, 7035–7045 (2006).
Google Scholar
Kang, J. S. et al. Docking of axonal mitochondria by syntaphilin controls their mobility and affects short-term facilitation. Cell 132, 137–148 (2008).
Google Scholar
Lewis, T. L. Jr, Kwon, S. K., Lee, A., Shaw, R. & Polleux, F. MFF-dependent mitochondrial fission regulates presynaptic release and axon branching by limiting axonal mitochondria size. Nat. Commun. 9, 5008 (2018).
Google Scholar
Verstreken, P. et al. Synaptic mitochondria are critical for mobilization of reserve pool vesicles at Drosophila neuromuscular junctions. Neuron 47, 365–378 (2005).
Google Scholar
Shields, L. Y. et al. Dynamin-related protein 1 is required for normal mitochondrial bioenergetic and synaptic function in CA1 hippocampal neurons. Cell Death Dis. 6, e1725 (2015).
Google Scholar
Horn, A., Raavicharla, S., Shah, S., Cox, D. & Jaiswal, J. K. Mitochondrial fragmentation enables localized signaling required for cell repair. J. Cell Biol. 219, e201909154 (2020).
Google Scholar
Wang, Y. et al. Mitochondrial fission promotes the continued clearance of apoptotic cells by macrophages. Cell 171, 331–345 (2017).
Google Scholar
Frank, S. et al. The role of dynamin-related protein 1, a mediator of mitochondrial fission, in apoptosis. Dev. Cell 1, 515–525 (2001).
Google Scholar
McArthur, K. et al. BAK/BAX macropores facilitate mitochondrial herniation and mtDNA efflux during apoptosis. Science 359, eaao6047 (2018).
Google Scholar
Prudent, J. et al. MAPL SUMOylation of Drp1 stabilizes an ER/mitochondrial platform required for cell death. Mol. Cell 59, 941–955 (2015).
Google Scholar
Nishimura, A. et al. Hypoxia-induced interaction of filamin with Drp1 causes mitochondrial hyperfission-associated myocardial senescence. Sci. Signal. 11, eaat5185 (2018).
Google Scholar
Ong, S. B. et al. Inhibiting mitochondrial fission protects the heart against ischemia/reperfusion injury. Circulation 121, 2012–2022 (2010).
Google Scholar
Sabouny, R. & Shutt, T. E. Reciprocal regulation of mitochondrial fission and fusion. Trends Biochem. Sci. 45, 564–577 (2020).
Google Scholar
Samangouei, P. et al. MiD49 and MiD51: new mediators of mitochondrial fission and novel targets for cardioprotection. Cond. Med. 1, 239–246 (2018).
Google Scholar
Zhou, H. et al. Mff-dependent mitochondrial fission contributes to the pathogenesis of cardiac microvasculature ischemia/reperfusion injury via induction of mROS-mediated cardiolipin oxidation and HK2/VDAC1 disassociation-involved mPTP opening. J. Am. Heart Assoc. 6, e005328 (2017).
Google Scholar
Civenni, G. et al. Epigenetic control of mitochondrial fission enables self-renewal of stem-like tumor cells in human prostate cancer. Cell Metab. 30, 303–318 (2019).
Google Scholar
Udagawa, O. & Ishihara, N. Mitochondrial dynamics and interorganellar communication in the development and dysmorphism of mammalian oocytes. J. Biochem. 167, 257–266 (2020).
Google Scholar
Tian, L. et al. Ischemia-induced Drp1 and Fis1-mediated mitochondrial fission and right ventricular dysfunction in pulmonary hypertension. J. Mol. Med. (Berl.) 95, 381–393 (2017).
Google Scholar
Humphries, B. A. et al. Enhanced mitochondrial fission suppresses signaling and metastasis in triple-negative breast cancer. Breast Cancer Res. 22, 60 (2020).
Google Scholar