Mitochondrial dynamics: overview of molecular mechanisms

Mitochondria are highly dynamic organelles undergoing coordinated cycles of fission and fusion, referred as ‘mitochondrial dynamics’, in order to maintain their shape, distribution and size. Their transient and rapid morphological adaptations are crucial for many cellular processes such as cell cycle, immunity, apoptosis and mitochondrial quality control. Mutations in the core machinery components and defects in mitochondrial dynamics have been associated with numerous human diseases. These dynamic transitions are mainly ensured by large GTPases belonging to the Dynamin family. Mitochondrial fission is a multi-step process allowing the division of one mitochondrion in two daughter mitochondria. It is regulated by the recruitment of the GTPase Dynamin-related protein 1 (Drp1) by adaptors at actin- and endoplasmic reticulum-mediated mitochondrial constriction sites. Drp1 oligomerization followed by mitochondrial constriction leads to the recruitment of Dynamin 2 to terminate membrane scission. Inner mitochondrial membrane constriction has been proposed to be an independent process regulated by calcium influx. Mitochondrial fusion is driven by a two-step process with the outer mitochondrial membrane fusion mediated by mitofusins 1 and 2 followed by inner membrane fusion, mediated by optic atrophy 1. In addition to the role of membrane lipid composition, several members of the machinery can undergo post-translational modifications modulating these processes. Understanding the molecular mechanisms controlling mitochondrial dynamics is crucial to decipher how mitochondrial shape meets the function and to increase the knowledge on the molecular basis of diseases associated with morphology defects. This article will describe an overview of the molecular mechanisms that govern mitochondrial fission and fusion in mammals.

[1]  Y. Adachi,et al.  An unstructured loop that is critical for interactions of the stalk domain of Drp1 with saturated phosphatidic acid , 2018, Small GTPases.

[2]  P. Fuchs,et al.  The heptad repeat domain 1 of Mitofusin has membrane destabilization function in mitochondrial fusion , 2018, EMBO reports.

[3]  Steven A. Brown,et al.  Circadian Control of DRP1 Activity Regulates Mitochondrial Dynamics and Bioenergetics. , 2018, Cell metabolism.

[4]  R. Youle,et al.  Mitophagy and Quality Control Mechanisms in Mitochondrial Maintenance , 2018, Current Biology.

[5]  Jeremy G. Wideman,et al.  A new mitofusin topology places the redox-regulated C terminus in the mitochondrial intermembrane space , 2018, The Journal of cell biology.

[6]  T. Meitinger,et al.  Extension of the phenotype of biallelic loss‐of‐function mutations in SLC25A46 to the severe form of pontocerebellar hypoplasia type I , 2018, Clinical genetics.

[7]  E. Morel,et al.  Mitochondrial Dynamics in Basal and Stressful Conditions , 2018, International journal of molecular sciences.

[8]  Dimitri Krainc,et al.  Mitochondria-lysosome contacts regulate mitochondrial fission via Rab7 GTP hydrolysis , 2018, Nature.

[9]  P. Chinnery,et al.  A novel mechanism causing imbalance of mitochondrial fusion and fission in human myopathies , 2018, Human molecular genetics.

[10]  H. Higgs,et al.  INF2-mediated actin polymerization at the ER stimulates mitochondrial calcium uptake, inner membrane constriction, and division , 2018, The Journal of cell biology.

[11]  S. Tenzer,et al.  The thiol switch C684 in Mitofusin-2 mediates redox-induced alterations of mitochondrial shape and respiration , 2017, Neurochemistry International.

[12]  Erika L. Pearce,et al.  Mitochondrial Dynamics at the Interface of Immune Cell Metabolism and Function. , 2018, Trends in immunology.

[13]  Y. Adachi,et al.  Phosphatidic Acid and Cardiolipin Coordinate Mitochondrial Dynamics. , 2018, Trends in cell biology.

[14]  L. Schoenfeld,et al.  Receptor-mediated Drp1 oligomerization on endoplasmic reticulum , 2017, bioRxiv.

[15]  W. Prinz,et al.  Sequences flanking the transmembrane segments facilitate mitochondrial localization and membrane fusion by mitofusin , 2017, Proceedings of the National Academy of Sciences.

[16]  C. Culmsee,et al.  Cofilin1-dependent actin dynamics control DRP1-mediated mitochondrial fission , 2017, Cell Death and Disease.

[17]  H. McBride,et al.  mTOR Controls Mitochondrial Dynamics and Cell Survival via MTFP1. , 2017, Molecular cell.

[18]  M. Ryan,et al.  The constriction and scission machineries involved in mitochondrial fission , 2017, Journal of Cell Science.

[19]  K. Mihara,et al.  Molecular basis of selective mitochondrial fusion by heterotypic action between OPA1 and cardiolipin , 2017, Nature Cell Biology.

[20]  Hyo Min Cho,et al.  Constriction of the mitochondrial inner compartment is a priming event for mitochondrial division , 2017, Nature Communications.

[21]  M. Zeviani,et al.  Recessive mutations in MSTO1 cause mitochondrial dynamics impairment, leading to myopathy and ataxia , 2017, Human mutation.

[22]  P. Várnai,et al.  MSTO1 is a cytoplasmic pro‐mitochondrial fusion protein, whose mutation induces myopathy and ataxia in humans , 2017, EMBO molecular medicine.

[23]  D. Chan,et al.  Mfn1 structures reveal nucleotide-triggered dimerization critical for mitochondrial fusion , 2017, Nature.

[24]  Z. Rao,et al.  Structures of human mitofusin 1 provide insight into mitochondrial tethering , 2016, The Journal of cell biology.

[25]  T. Saigusa,et al.  Mitochondrial division occurs concurrently with autophagosome formation but independently of Drp1 during mitophagy , 2016, The Journal of cell biology.

[26]  G. Dorn,et al.  Correcting mitochondrial fusion by manipulating mitofusin conformations , 2016, Nature.

[27]  H. Han,et al.  Aβ-Induced Drp1 phosphorylation through Akt activation promotes excessive mitochondrial fission leading to neuronal apoptosis. , 2016, Biochimica et biophysica acta.

[28]  G. Voeltz,et al.  Multiple Dynamin family members collaborate to drive mitochondrial division , 2016, Nature.

[29]  Shangcheng Xu,et al.  CaMKII induces permeability transition through Drp1 phosphorylation during chronic β-AR stimulation , 2016, Nature Communications.

[30]  E. Holzbaur,et al.  Dynamic actin cycling through mitochondrial subpopulations locally regulates the fission–fusion balance within mitochondrial networks , 2016, Nature Communications.

[31]  Kara L. Cerveny,et al.  Coincident Phosphatidic Acid Interaction Restrains Drp1 in Mitochondrial Division. , 2016, Molecular cell.

[32]  J. Nunnari,et al.  ER-mitochondria contacts couple mtDNA synthesis with mitochondrial division in human cells , 2016, Science.

[33]  E. Shoubridge,et al.  SLC25A46 is required for mitochondrial lipid homeostasis and cristae maintenance and is responsible for Leigh syndrome , 2016, EMBO molecular medicine.

[34]  E. Sell,et al.  DNM1L-related mitochondrial fission defect presenting as refractory epilepsy , 2015, European Journal of Human Genetics.

[35]  T. Langer,et al.  OPA1 processing in cell death and disease – the long and short of it , 2016, Journal of Cell Science.

[36]  W. Kühlbrandt,et al.  A mitofusin-dependent docking ring complex triggers mitochondrial fusion in vitro , 2016, eLife.

[37]  D. Stojanovski,et al.  Cooperative and independent roles of the Drp1 adaptors Mff, MiD49 and MiD51 in mitochondrial fission , 2016, Journal of Cell Science.

[38]  J. Olivo-Marin,et al.  A role for septin 2 in Drp1‐mediated mitochondrial fission , 2016, EMBO reports.

[39]  S. Scherer,et al.  Lethal Disorder of Mitochondrial Fission Caused by Mutations in DNM1L. , 2016, The Journal of pediatrics.

[40]  L. Scorrano,et al.  Mitochondrial Cristae: Where Beauty Meets Functionality. , 2016, Trends in biochemical sciences.

[41]  K. Mihara,et al.  Drp1-dependent mitochondrial fission via MiD49/51 is essential for apoptotic cristae remodeling , 2016, The Journal of cell biology.

[42]  Prashant Mishra,et al.  Metabolic regulation of mitochondrial dynamics , 2016, The Journal of cell biology.

[43]  L. Scorrano,et al.  Mito-Morphosis: Mitochondrial Fusion, Fission, and Cristae Remodeling as Key Mediators of Cellular Function. , 2016, Annual review of physiology.

[44]  T. Wai,et al.  Mitochondrial Dynamics and Metabolic Regulation , 2016, Trends in Endocrinology & Metabolism.

[45]  H. Prokisch,et al.  Disturbed mitochondrial and peroxisomal dynamics due to loss of MFF causes Leigh-like encephalopathy, optic atrophy and peripheral neuropathy , 2016, Journal of Medical Genetics.

[46]  F. Polleux,et al.  AMP-activated protein kinase mediates mitochondrial fission in response to energy stress , 2016, Science.

[47]  W. Lederer,et al.  Mitochondrial E3 ubiquitin ligase MARCH5 controls mitochondrial fission and cell sensitivity to stress-induced apoptosis through regulation of MiD49 protein , 2016, Molecular biology of the cell.

[48]  Á. Raya,et al.  Early ERK1/2 activation promotes DRP1-dependent mitochondrial fission necessary for cell reprogramming , 2015, Nature Communications.

[49]  D. Chan,et al.  The mitochondrial fission receptor Mff selectively recruits oligomerized Drp1 , 2015, Molecular biology of the cell.

[50]  H. Higgs,et al.  Actin filaments target the oligomeric maturation of the dynamin GTPase Drp1 to mitochondrial fission sites , 2015, eLife.

[51]  J. Mears,et al.  Distinct Splice Variants of Dynamin-related Protein 1 Differentially Utilize Mitochondrial Fission Factor as an Effector of Cooperative GTPase Activity* , 2015, The Journal of Biological Chemistry.

[52]  H. McBride,et al.  MAPL SUMOylation of Drp1 Stabilizes an ER/Mitochondrial Platform Required for Cell Death. , 2015, Molecular cell.

[53]  J. Mears,et al.  Cardiolipin's propensity for phase transition and its reorganization by dynamin-related protein 1 form a basis for mitochondrial membrane fission , 2015, Molecular biology of the cell.

[54]  V. Mootha,et al.  The molecular era of the mitochondrial calcium uniporter , 2015, Nature Reviews Molecular Cell Biology.

[55]  J. Lippincott-Schwartz,et al.  A mitochondria-anchored isoform of the actin-nucleating spire protein regulates mitochondrial division , 2015, eLife.

[56]  Michael T Ryan,et al.  Analysis of ER–mitochondria contacts using correlative fluorescence microscopy and soft X-ray tomography of mammalian cells , 2015, Journal of Cell Science.

[57]  R. Schüle,et al.  Mutations in the UGO1-like protein SLC25A46 cause an optic atrophy spectrum disorder , 2015, Nature Genetics.

[58]  L. Scorrano,et al.  Extracellular Regulated Kinase Phosphorylates Mitofusin 1 to Control Mitochondrial Morphology and Apoptosis , 2015, Molecular cell.

[59]  Elisa Greotti,et al.  Mitofusin 2 ablation increases endoplasmic reticulum–mitochondria coupling , 2015, Proceedings of the National Academy of Sciences.

[60]  J. Mears,et al.  The Mechanoenzymatic Core of Dynamin-related Protein 1 Comprises the Minimal Machinery Required for Membrane Constriction* , 2015, The Journal of Biological Chemistry.

[61]  K. Hoehn,et al.  Erk2 phosphorylation of Drp1 promotes mitochondrial fission and MAPK-driven tumor growth. , 2015, Molecular cell.

[62]  J. Chipuk,et al.  Mitochondrial division is requisite to RAS-induced transformation and targeted by oncogenic MAPK pathway inhibitors. , 2015, Molecular cell.

[63]  Ting Li,et al.  Blockage of GSK3β-mediated Drp1 phosphorylation provides neuroprotection in neuronal and mouse models of Alzheimer's disease , 2015, Neurobiology of Aging.

[64]  W. Lederer,et al.  Transient assembly of F-actin on the outer mitochondrial membrane contributes to mitochondrial fission , 2015, The Journal of cell biology.

[65]  J. Vance.  Phospholipid Synthesis and Transport in Mammalian Cells , 2015, Traffic.

[66]  Sujin Choi,et al.  MFN1 deacetylation activates adaptive mitochondrial fusion and protects metabolically challenged mitochondria , 2014, Journal of Cell Science.

[67]  Shang-Yi Chiu,et al.  Disruption of SUMO-Specific Protease 2 Induces Mitochondria Mediated Neurodegeneration , 2014, PLoS genetics.

[68]  H. McBride,et al.  A new pathway for mitochondrial quality control: mitochondrial‐derived vesicles , 2014, The EMBO journal.

[69]  W. Nickel,et al.  Dynamin-related Protein 1 (Drp1) Promotes Structural Intermediates of Membrane Division* , 2014, The Journal of Biological Chemistry.

[70]  J. Martinou,et al.  Specific Interaction with Cardiolipin Triggers Functional Activation of Dynamin-Related Protein 1 , 2014, PloS one.

[71]  J. Mears,et al.  A dimeric equilibrium intermediate nucleates Drp1 reassembly on mitochondrial membranes for fission , 2014, Molecular biology of the cell.

[72]  Prashant Mishra,et al.  Proteolytic cleavage of Opa1 stimulates mitochondrial inner membrane fusion and couples fusion to oxidative phosphorylation. , 2014, Cell metabolism.

[73]  Hyeseong Cho,et al.  MARCH5-mediated quality control on acetylated Mfn1 facilitates mitochondrial homeostasis and cell survival , 2014, Cell Death and Disease.

[74]  E. Rugarli,et al.  The i-AAA protease YME1L and OMA1 cleave OPA1 to balance mitochondrial fusion and fission , 2014, The Journal of cell biology.

[75]  H. Nakanishi,et al.  Phosphatidic Acid (PA)-preferring Phospholipase A1 Regulates Mitochondrial Dynamics* , 2014, The Journal of Biological Chemistry.

[76]  D. Chan,et al.  The mitochondrial fission receptor MiD51 requires ADP as a cofactor. , 2014, Structure.

[77]  K. Elgass,et al.  Structural and functional analysis of MiD51, a dynamin receptor required for mitochondrial fission , 2014, The Journal of cell biology.

[78]  H. Higgs,et al.  A Role for Myosin II in Mammalian Mitochondrial Fission , 2014, Current Biology.

[79]  H. McBride,et al.  ROMO1 Is an Essential Redox-Dependent Regulator of Mitochondrial Dynamics , 2014, Science Signaling.

[80]  Maria Markaki,et al.  Crosstalk between apoptosis, necrosis and autophagy. , 2013, Biochimica et biophysica acta.

[81]  S. Lipton,et al.  S-nitrosylation of dynamin-related protein 1 mediates mutant huntingtin-induced mitochondrial fragmentation and neuronal injury in Huntington's disease. , 2013, Antioxidants & redox signaling.

[82]  K. Elgass,et al.  Adaptor Proteins MiD49 and MiD51 Can Act Independently of Mff and Fis1 in Drp1 Recruitment and Are Specific for Mitochondrial Fission* , 2013, The Journal of Biological Chemistry.

[83]  H. McBride,et al.  MITOL regulates endoplasmic reticulum-mitochondria contacts via Mitofusin2. , 2013, Molecular cell.

[84]  K. Mihara,et al.  Dynamics of nucleoid structure regulated by mitochondrial fission contributes to cristae reformation and release of cytochrome c , 2013, Proceedings of the National Academy of Sciences.

[85]  P. Walter,et al.  ER-associated mitochondrial division links the distribution of mitochondria and mitochondrial DNA in yeast , 2013, eLife.

[86]  D. Schwefel,et al.  Structural insights into oligomerization and mitochondrial remodelling of dynamin 1‐like protein , 2013, The EMBO journal.

[87]  K. Mihara,et al.  New insights into the function and regulation of mitochondrial fission. , 2013, Biochimica et biophysica acta.

[88]  G. Dorn,et al.  PINK1-Phosphorylated Mitofusin 2 Is a Parkin Receptor for Culling Damaged Mitochondria , 2013, Science.

[89]  Adam Frost,et al.  Interchangeable adaptors regulate mitochondrial dynamin assembly for membrane scission , 2013, Proceedings of the National Academy of Sciences.

[90]  J. Henley,et al.  SENP3-mediated deSUMOylation of dynamin-related protein 1 promotes cell death following ischaemia , 2013, The EMBO journal.

[91]  Stefan Strack,et al.  A Calcineurin Docking Motif (LXVP) in Dynamin-related Protein 1 Contributes to Mitochondrial Fragmentation and Ischemic Neuronal Injury* , 2013, The Journal of Biological Chemistry.

[92]  D. Chan,et al.  Fis1, Mff, MiD49, and MiD51 mediate Drp1 recruitment in mitochondrial fission , 2013, Molecular biology of the cell.

[93]  H. Higgs,et al.  An Actin-Dependent Step in Mitochondrial Fission Mediated by the ER-Associated Formin INF2 , 2013, Science.

[94]  S. Strack,et al.  Reversible phosphorylation of Drp 1 by cyclic AMP-dependent protein kinase and calcineurin regulates mitochondrial fission and cell death , 2013 .

[95]  S. Howng,et al.  GSK3beta-Mediated Drp1 Phosphorylation Induced Elongated Mitochondrial Morphology against Oxidative Stress , 2012, PloS one.

[96]  G. Franck.  Open access , 2012, Cell cycle.

[97]  H. McBride,et al.  The intracellular redox state is a core determinant of mitochondrial fusion , 2012, EMBO reports.

[98]  C. Hoppel,et al.  Mitochondrial Division in Rat Cardiomyocytes: An Electron Microscope Study , 2011, Anatomical record.

[99]  T. Veenstra,et al.  Stress-induced phosphorylation and proteasomal degradation of mitofusin 2 facilitates mitochondrial fragmentation and apoptosis. , 2012, Molecules and Cells.

[100]  J. Yates,et al.  Modulation of Dynamin-related Protein 1 (DRP1) Function by Increased O-linked-β-N-acetylglucosamine Modification (O-GlcNAc) in Cardiac Myocytes* , 2012, The Journal of Biological Chemistry.

[101]  N. Pfanner,et al.  Mgr2 promotes coupling of the mitochondrial presequence translocase to partner complexes , 2012, The Journal of cell biology.

[102]  J. Nunnari,et al.  Mitochondria: In Sickness and in Health , 2012, Cell.

[103]  P. Overbeek,et al.  Mitochondrial fission triggered by hyperglycemia is mediated by ROCK1 activation in podocytes and endothelial cells. , 2012, Cell metabolism.

[104]  Xiaodong Wang,et al.  The Mitochondrial Phosphatase PGAM5 Functions at the Convergence Point of Multiple Necrotic Death Pathways , 2012, Cell.

[105]  Pietro De Camilli,et al.  Dynamin, a membrane-remodelling GTPase , 2012, Nature Reviews Molecular Cell Biology.

[106]  G. Mollet,et al.  INF2 mutations in Charcot-Marie-Tooth disease with glomerulopathy. , 2011, The New England journal of medicine.

[107]  Matthew West,et al.  ER Tubules Mark Sites of Mitochondrial Division , 2011, Science.

[108]  T. Langer,et al.  Quality control of mitochondrial proteostasis. , 2011, Cold Spring Harbor perspectives in biology.

[109]  O. Shupliakov,et al.  Human MIEF1 recruits Drp1 to mitochondrial outer membranes and promotes mitochondrial fusion rather than fission , 2011, The EMBO journal.

[110]  J. Lippincott-Schwartz,et al.  Tubular network formation protects mitochondria from autophagosomal degradation during nutrient starvation , 2011, Proceedings of the National Academy of Sciences.

[111]  Ann E. Frazier,et al.  MiD49 and MiD51, new components of the mitochondrial fission machinery , 2011, EMBO reports.

[112]  Y. Yoon,et al.  Control of Mitochondrial Morphology Through Differential Interactions of Mitochondrial Fusion and Fission Proteins , 2011, PloS one.

[113]  H. Ren,et al.  piRNA-associated germline nuage formation and spermatogenesis require MitoPLD profusogenic mitochondrial-surface lipid signaling. , 2011, Developmental cell.

[114]  Min Liu,et al.  Parkin Ubiquitinates Drp1 for Proteasome-dependent Degradation , 2011, The Journal of Biological Chemistry.

[115]  L. Scorrano,et al.  During autophagy mitochondria elongate, are spared from degradation and sustain cell viability , 2011, Nature Cell Biology.

[116]  G. Mollet,et al.  Mutations in INF2 are a major cause of autosomal dominant focal segmental glomerulosclerosis. , 2011, Journal of the American Society of Nephrology : JASN.

[117]  Soojay Banerjee,et al.  The soluble form of Bax regulates mitochondrial fusion via MFN2 homotypic complexes. , 2011, Molecular cell.

[118]  R. Sobel,et al.  Aberrant mitochondrial fission in neurons induced by protein kinase Cδ under oxidative stress conditions in vivo , 2011, Molecular biology of the cell.

[119]  J. Mears,et al.  Conformational changes in Dnm1 support a contractile mechanism for mitochondrial fission , 2010, Nature Structural &Molecular Biology.

[120]  D. Selkoe.  Alzheimer's disease. , 2011, Cold Spring Harbor perspectives in biology.

[121]  R. Youle,et al.  Mff is an essential factor for mitochondrial recruitment of Drp1 during mitochondrial fission in mammalian cells , 2010, The Journal of cell biology.

[122]  A. B. Knott,et al.  S-Nitrosylation of DRP1 does not affect enzymatic activity and is not specific to Alzheimer's disease. , 2010, Journal of Alzheimer's disease : JAD.

[123]  J. Heymann,et al.  OPA1 disease alleles causing dominant optic atrophy have defects in cardiolipin-stimulated GTP hydrolysis and membrane tubulation , 2010, Human molecular genetics.

[124]  D. Turnbull,et al.  Multi-system neurological disease is common in patients with OPA1 mutations , 2010, Brain : a journal of neurology.

[125]  A. B. Knott,et al.  S-Nitrosylation of DRP 1 Does Not Affect Enzymatic Activity and is Not Specific to Alzheimer ’ s Disease , 2010 .

[126]  A. M. van der Bliek,et al.  Inducible proteolytic inactivation of OPA1 mediated by the OMA1 protease in mammalian cells , 2009, The Journal of cell biology.

[127]  E. Rugarli,et al.  Regulation of OPA1 processing and mitochondrial fusion by m-AAA protease isoenzymes and OMA1 , 2009, The Journal of cell biology.

[128]  C. Sachse,et al.  Structure of a Bacterial Dynamin-like Protein Lipid Tube Provides a Mechanism For Assembly and Membrane Curving , 2009, Cell.

[129]  Rachel M. Devay,et al.  Coassembly of Mgm1 isoforms requires cardiolipin and mediates mitochondrial inner membrane fusion , 2009, The Journal of cell biology.

[130]  T. Kensler,et al.  The dynamin-related GTPase Drp1 is required for embryonic and brain development in mice , 2009, The Journal of cell biology.

[131]  J. Rubinstein,et al.  Phospholipid Association Is Essential for Dynamin-related Protein Mgm1 to Function in Mitochondrial Membrane Fusion* , 2009, The Journal of Biological Chemistry.

[132]  J. McCaffery,et al.  Mitofusins and OPA1 mediate sequential steps in mitochondrial membrane fusion. , 2009, Molecular biology of the cell.

[133]  Satoshi O. Suzuki,et al.  Mitochondrial fission factor Drp1 is essential for embryonic development and synapse formation in mice , 2009, Nature Cell Biology.

[134]  H. McBride,et al.  MAPL is a new mitochondrial SUMO E3 ligase that regulates mitochondrial fission , 2009, EMBO reports.

[135]  Marc Liesa,et al.  Mitochondrial dynamics in mammalian health and disease. , 2009, Physiological reviews.

[136]  Jean-Claude Martinou,et al.  SLP‐2 is required for stress‐induced mitochondrial hyperfusion , 2009, The EMBO journal.

[137]  H. McBride,et al.  Translocation of SenP5 from the Nucleoli to the Mitochondria Modulates DRP1-dependent Fission during Mitosis* , 2009, The Journal of Biological Chemistry.

[138]  A. Godzik,et al.  S-Nitrosylation of Drp1 Mediates β-Amyloid-Related Mitochondrial Fission and Neuronal Injury , 2009, Science.

[139]  J. McCaffery,et al.  Mitochondrial outer and inner membrane fusion requires a modified carrier protein , 2009, The Journal of cell biology.

[140]  L. Scorrano,et al.  Mitofusin 2 tethers endoplasmic reticulum to mitochondria , 2008, Nature.

[141]  P. Bernardi,et al.  Dephosphorylation by calcineurin regulates translocation of Drp1 to mitochondria , 2008, Proceedings of the National Academy of Sciences.

[142]  A. M. van der Bliek,et al.  The novel tail-anchored membrane protein Mff controls mitochondrial and peroxisomal fission in mammalian cells. , 2008, Molecular biology of the cell.

[143]  Robert W. Taylor,et al.  Mutation of OPA1 causes dominant optic atrophy with external ophthalmoplegia, ataxia, deafness and multiple mitochondrial DNA deletions: a novel disorder of mtDNA maintenance. , 2008, Brain : a journal of neurology.

[144]  R. Schwarzenbacher,et al.  OPA1 mutations induce mitochondrial DNA instability and optic atrophy 'plus' phenotypes. , 2008, Brain : a journal of neurology.

[145]  S. Strack,et al.  Reversible phosphorylation of Drp1 by cyclic AMP‐dependent protein kinase and calcineurin regulates mitochondrial fission and cell death , 2007, EMBO reports.

[146]  A. M. van der Bliek,et al.  Regulation of the mitochondrial dynamin-like protein Opa1 by proteolytic cleavage , 2007, The Journal of cell biology.

[147]  D. Chan,et al.  OPA1 processing controls mitochondrial fusion and is regulated by mRNA splicing, membrane potential, and Yme1L , 2007, The Journal of cell biology.

[148]  Y. Yoon,et al.  Thapsigargin induces biphasic fragmentation of mitochondria through calcium‐mediated mitochondrial fission and apoptosis , 2007, Journal of cellular physiology.

[149]  C. Blackstone,et al.  Cyclic AMP-dependent Protein Kinase Phosphorylation of Drp1 Regulates Its GTPase Activity and Mitochondrial Morphology* , 2007, Journal of Biological Chemistry.

[150]  R. Youle,et al.  The mitochondrial E3 ubiquitin ligase MARCH5 is required for Drp1 dependent mitochondrial division , 2007, The Journal of cell biology.

[151]  Jennifer R. Davies,et al.  Opa1 deficiency in a mouse model of autosomal dominant optic atrophy impairs mitochondrial morphology, optic nerve structure and visual function. , 2007, Human molecular genetics.

[152]  H. McBride,et al.  Bax/Bak promote sumoylation of DRP1 and its stable association with mitochondria during apoptotic cell death , 2007, The Journal of cell biology.

[153]  H. Waterham,et al.  A lethal defect of mitochondrial and peroxisomal fission. , 2007, The New England journal of medicine.

[154]  Toshihiko Oka,et al.  Mitotic Phosphorylation of Dynamin-related GTPase Drp1 Participates in Mitochondrial Fission* , 2007, Journal of Biological Chemistry.

[155]  Seok-Yong Choi,et al.  A common lipid links Mfn-mediated mitochondrial fusion and SNARE-regulated exocytosis , 2006, Nature Cell Biology.

[156]  H. McBride,et al.  Mitochondria: More Than Just a Powerhouse , 2006, Current Biology.

[157]  Sara Cipolat,et al.  OPA1 Controls Apoptotic Cristae Remodeling Independently from Mitochondrial Fusion , 2006, Cell.

[158]  V. Mils,et al.  Mitochondrial dynamics and disease, OPA1. , 2006, Biochimica et biophysica acta.

[159]  J. Hinshaw,et al.  Mdv1 Interacts with Assembled Dnm1 to Promote Mitochondrial Division* , 2006, Journal of Biological Chemistry.

[160]  A. Beggs,et al.  Mutations in dynamin 2 cause dominant centronuclear myopathy , 2005, Nature Genetics.

[161]  J. McCaffery,et al.  Dnm1 forms spirals that are structurally tailored to fit mitochondria , 2005, The Journal of cell biology.

[162]  Axel Niemann,et al.  Ganglioside-induced differentiation associated protein 1 is a regulator of the mitochondrial network , 2005, The Journal of cell biology.

[163]  Erik E. Griffin,et al.  The WD40 protein Caf4p is a component of the mitochondrial fission machinery and recruits Dnm1p to mitochondria , 2005, The Journal of cell biology.

[164]  A. Santel,et al.  The mitochondrial protein MTP18 contributes to mitochondrial fission in mammalian cells , 2005, Journal of Cell Science.

[165]  P. Amati‐Bonneau,et al.  eOPA1: An online database for OPA1 mutations , 2005, Human mutation.

[166]  Danqing Zhu,et al.  Mutations in the pleckstrin homology domain of dynamin 2 cause dominant intermediate Charcot-Marie-Tooth disease , 2005, Nature Genetics.

[167]  A. Beggs,et al.  Mutations in dynamin 2 cause dominant centronuclear myopathy. , 2005, Nature genetics.

[168]  Erik E. Griffin,et al.  The WD 40 protein Caf 4 p is a component of the mitochondrial fission machinery and recruits Dnm 1 p to mitochondria , 2005 .

[169]  K. Mihara,et al.  Mitofusin 1 and 2 play distinct roles in mitochondrial fusion reactions via GTPase activity , 2004, Journal of Cell Science.

[170]  L. Scorrano,et al.  OPA1 requires mitofusin 1 to promote mitochondrial fusion. , 2004, Proceedings of the National Academy of Sciences of the United States of America.

[171]  J. McCaffery,et al.  Structural Basis of Mitochondrial Tethering by Mitofusin Complexes , 2004, Science.

[172]  A. Klippel,et al.  Knockdown of MTP18, a Novel Phosphatidylinositol 3-Kinase-dependent Protein, Affects Mitochondrial Morphology and Induces Apoptosis* , 2004, Journal of Biological Chemistry.

[173]  R. Jensen,et al.  Ugo1p Links the Fzo1p and Mgm1p GTPases for Mitochondrial Fusion* , 2004, Journal of Biological Chemistry.

[174]  M. Pericak-Vance,et al.  Mutations in the mitochondrial GTPase mitofusin 2 cause Charcot-Marie-Tooth neuropathy type 2A , 2004, Nature Genetics.

[175]  A. M. van der Bliek,et al.  Loss of the Intermembrane Space Protein Mgm1/OPA1 Induces Swelling and Localized Constrictions along the Lengths of Mitochondria* , 2004, Journal of Biological Chemistry.

[176]  K. Hayasaka,et al.  Mitochondrial GTPase mitofusin 2 mutation in Charcot–Marie–Tooth neuropathy type 2A , 2004, Human Genetics.

[177]  K. Mihara,et al.  Two mitofusin proteins, mammalian homologues of FZO, with distinct functions are both required for mitochondrial fusion. , 2003, Journal of biochemistry.

[178]  R. Jensen,et al.  Mgm1p, a dynamin-related GTPase, is essential for fusion of the mitochondrial outer membrane. , 2003, Molecular biology of the cell.

[179]  B. Allf,et al.  Hereditary motor and sensory neuropathy type VI with optic atrophy. , 2003, American journal of ophthalmology.

[180]  M. Schrader,et al.  Dynamin-like Protein 1 Is Involved in Peroxisomal Fission* , 2003, The Journal of Biological Chemistry.

[181]  Erik E. Griffin,et al.  Mitofusins Mfn1 and Mfn2 coordinately regulate mitochondrial fusion and are essential for embryonic development , 2003, The Journal of cell biology.

[182]  P. Frachon,et al.  Mitochondrial fusion in human cells is efficient, requires the inner membrane potential, and is mediated by mitofusins. , 2002, Molecular biology of the cell.

[183]  G. Lenaers,et al.  The human dynamin‐related protein OPA1 is anchored to the mitochondrial inner membrane facing the inter‐membrane space , 2002, FEBS letters.

[184]  A. Lombès,et al.  Membrane topology and mitochondrial targeting of mitofusins, ubiquitous mammalian homologs of the transmembrane GTPase Fzo. , 2002, Journal of cell science.

[185]  I. Marín,et al.  The gene encoding ganglioside-induced differentiation-associated protein 1 is mutated in axonal Charcot-Marie-Tooth type 4A disease , 2002, Nature Genetics.

[186]  J. Gilbert,et al.  Ganglioside-induced differentiation-associated protein-1 is mutant in Charcot-Marie-Tooth disease type 4A/8q21 , 2002, Nature Genetics.

[187]  M. McNiven,et al.  Mammalian dynamin-like protein DLP1 tubulates membranes. , 2001, Molecular biology of the cell.

[188]  A. M. van der Bliek,et al.  Dynamin-related protein Drp1 is required for mitochondrial division in mammalian cells. , 2001, Molecular biology of the cell.

[189]  A. Santel,et al.  Control of mitochondrial morphology by a human mitofusin. , 2001, Journal of cell science.

[190]  J. Nunnari,et al.  Mdv1p Is a Wd Repeat Protein That Interacts with the Dynamin-Related Gtpase, Dnm1p, to Trigger Mitochondrial Division , 2000, The Journal of cell biology.

[191]  J. Shaw,et al.  Dnm1p Gtpase-Mediated Mitochondrial Fission Is a Multi-Step Process Requiring the Novel Integral Membrane Component Fis1p , 2000, The Journal of cell biology.

[192]  J. Grosgeorge,et al.  Nuclear gene OPA1, encoding a mitochondrial dynamin-related protein, is mutated in dominant optic atrophy , 2000, Nature Genetics.

[193]  S. Bhattacharya,et al.  OPA1, encoding a dynamin-related GTPase, is mutated in autosomal dominant optic atrophy linked to chromosome 3q28 , 2000, Nature Genetics.

[194]  R. Jensen,et al.  Division versus Fusion: Dnm1p and Fzo1p Antagonistically Regulate Mitochondrial Shape , 1999, The Journal of cell biology.

[195]  A. M. van der Bliek,et al.  C. elegans dynamin-related protein DRP-1 controls severing of the mitochondrial outer membrane. , 1999, Molecular cell.

[196]  J. Shaw,et al.  The dynamin-related GTPase Dnm1 regulates mitochondrial fission in yeast , 1999, Nature Cell Biology.

[197]  J. Thatcher,et al.  Mitochondrial Fusion in Yeast Requires the Transmembrane GTPase Fzo1p , 1998, The Journal of cell biology.

[198]  K. G. Hales,et al.  Developmentally Regulated Mitochondrial Fusion Mediated by a Conserved, Novel, Predicted GTPase , 1997, Cell.