Mfn2

Summary

Gene Symbol: Mfn2
Description: mitofusin 2
Alias: D630023P19Rik, Fzo, mitofusin-2, HSG protein, hypertension related protein 1, mitochondrial assembly regulatory factor, transmembrane GTPase MFN2
Species: mouse

Top Publications

  1. pmc Mitofusins Mfn1 and Mfn2 coordinately regulate mitochondrial fusion and are essential for embryonic development
    Hsiuchen Chen
    Division of Biology, Beckman Institute, California Institute of Technology, Pasadena, CA 91125, USA
    J Cell Biol 160:189-200. 2003
  2. pmc Mitofusin 2-containing mitochondrial-reticular microdomains direct rapid cardiomyocyte bioenergetic responses via interorganelle Ca(2+) crosstalk
    Yun Chen
    Center for Pharmacogenomics, Department of Internal Medicine, Washington University School of Medicine, St Louis, MO 63110, USA
    Circ Res 111:863-75. 2012
  3. pmc Mitofusin 2 in POMC neurons connects ER stress with leptin resistance and energy imbalance
    Marc Schneeberger
    Diabetes and Obesity Research Laboratory, Institut d Investigacions Biomediques August Pi i Sunyer IDIBAPS, 08036 Barcelona, Spain Department of Endocrinology and Nutrition, Hospital Clínic School of Medicine, University of Barcelona, 08036 Barcelona, Spain Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas Asociadas CIBERDEM, 08036 Barcelona, Spain
    Cell 155:172-87. 2013
  4. doi Mitochondrial fusion directs cardiomyocyte differentiation via calcineurin and Notch signaling
    Atsuko Kasahara
    Department of Cell Physiology and Metabolism, University of Geneva, 1206 Geneva, Switzerland
    Science 342:734-7. 2013
  5. pmc Loss of mitofusin 2 promotes endoplasmic reticulum stress
    Gladys A Ngoh
    Whitaker Cardiovascular Institute, Boston University School of Medicine, Boston, Massachusetts 02118, USA
    J Biol Chem 287:20321-32. 2012
  6. pmc Mitofusin 2 (Mfn2) links mitochondrial and endoplasmic reticulum function with insulin signaling and is essential for normal glucose homeostasis
    David Sebastian
    Institute for Research in Biomedicine IRB Barcelona, 08028 Barcelona, Spain
    Proc Natl Acad Sci U S A 109:5523-8. 2012
  7. pmc Mitochondrial fusion is essential for organelle function and cardiac homeostasis
    Yun Chen
    Center for Pharmacogenomics, Department of Internal Medicine, Washington University School of Medicine, St Louis, MO 63110, USA
    Circ Res 109:1327-31. 2011
  8. pmc Control of mitochondrial morphology through differential interactions of mitochondrial fusion and fission proteins
    Pinwei Huang
    Mitochondrial Research and Innovation Group, Department of Anesthesiology, University of Rochester School of Medicine and Dentistry, Rochester, New York, United States of America
    PLoS ONE 6:e20655. 2011
  9. pmc Mitofusin-2 maintains mitochondrial structure and contributes to stress-induced permeability transition in cardiac myocytes
    Kyriakos N Papanicolaou
    Molecular Cardiology Whitaker Cardiovascular Institute, Boston University School of Medicine, 715 Albany Street, W611, Boston, MA 02118, USA
    Mol Cell Biol 31:1309-28. 2011
  10. pmc Mitochondrial fusion is required for mtDNA stability in skeletal muscle and tolerance of mtDNA mutations
    Hsiuchen Chen
    Division of Biology, California Institute of Technology, Pasadena, CA 91125, USA
    Cell 141:280-9. 2010

Research Grants

Scientific Experts

  • Paritosh Ghosh
  • M Beresewicz
  • Alina Ainbinder
  • Marcelo O Dietrich
  • GERALD DORN
  • Pierre Cosson
  • Takumi Koshiba
  • Aaron Waxman
  • Mariusz Karbowski
  • A Wagatsuma
  • Manuel Rojo
  • David C Chan
  • Yun Chen
  • Hsiuchen Chen
  • Marc Liesa
  • Antonio Zorzano
  • Kyriakos N Papanicolaou
  • Arnaud Mourier
  • Maria Kawalec
  • Olga Martins de Brito
  • Jonathan M Gall
  • Manuel Palacin
  • David Sebastian
  • Gladys A Ngoh
  • Luca Scorrano
  • J Michael McCaffery
  • Craig Brooks
  • Nils Goran Larsson
  • Anh H Pham
  • Juan Pablo Munoz
  • Kenneth Walsh
  • Zhiyin Song
  • Naotada Ishihara
  • Maria Fernanda Forni
  • Eduardo Silva Ramos
  • T G Biel
  • Larry L Luchsinger
  • Yongping Zhang
  • Junghyung Park
  • Wenzhang Wang
  • Riccardo Filadi
  • Prashant Mishra
  • Seung Wook Ryu
  • Barbara Zabłocka
  • Aditi Sood
  • Orian Shirihai
  • Brian G Drew
  • Wen Yue
  • Zhaofei Wu
  • Steven C Borkan
  • Zhiyong Wang
  • Scott A Detmer
  • Andrea Havasi
  • Ying Zhang
  • Marc Schneeberger
  • Quan Chen
  • Atsuko Kasahara
  • Ayumu Sugiura
  • Xiaohu Huang
  • María Isabel Hernández-Alvarez
  • Francesc X Soriano
  • William H Eschenbacher
  • Ting Zhao
  • Seungmin Lee
  • Guang ju Zhao
  • Jia Li
  • Russell S Whelan
  • Yingqiu Liu
  • William C Stanley
  • Pinwei Huang
  • Virginie Guillet
  • Karthika Singaravelu
  • Daniel Bach
  • Suzanne Hoppins
  • Albert Misko
  • Jean Claude Martinou
  • Yuquan Li
  • Kai Yasukawa
  • Daniel Tondera
  • Takuma Uo
  • Xiaolin Chen
  • Zheng Dong
  • Nuria Lopez-Bigas
  • Sara Pich
  • Anne Chomyn
  • Patrycja Pawlikowska
  • Lu Fang
  • Guang Jian Jiang
  • Ken S Wang
  • Shinji Honda

Detail Information

Publications79

  1. pmc Mitofusins Mfn1 and Mfn2 coordinately regulate mitochondrial fusion and are essential for embryonic development
    Hsiuchen Chen
    Division of Biology, Beckman Institute, California Institute of Technology, Pasadena, CA 91125, USA
    J Cell Biol 160:189-200. 2003
    ..The mitofusins, Mfn1 and Mfn2, have been shown to affect mitochondrial morphology when overexpressed...
  2. pmc Mitofusin 2-containing mitochondrial-reticular microdomains direct rapid cardiomyocyte bioenergetic responses via interorganelle Ca(2+) crosstalk
    Yun Chen
    Center for Pharmacogenomics, Department of Internal Medicine, Washington University School of Medicine, St Louis, MO 63110, USA
    Circ Res 111:863-75. 2012
    ..Mitofusin (Mfn) 1 and 2 mediate mitochondrial outer membrane fusion, whereas Mfn2 but not Mfn1 tethers endoplasmic reticulum to mitochondria in noncardiac cells.
  3. pmc Mitofusin 2 in POMC neurons connects ER stress with leptin resistance and energy imbalance
    Marc Schneeberger
    Diabetes and Obesity Research Laboratory, Institut d Investigacions Biomediques August Pi i Sunyer IDIBAPS, 08036 Barcelona, Spain Department of Endocrinology and Nutrition, Hospital Clínic School of Medicine, University of Barcelona, 08036 Barcelona, Spain Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas Asociadas CIBERDEM, 08036 Barcelona, Spain
    Cell 155:172-87. 2013
    b>Mitofusin 2 (MFN2) plays critical roles in both mitochondrial fusion and the establishment of mitochondria-endoplasmic reticulum (ER) interactions...
  4. doi Mitochondrial fusion directs cardiomyocyte differentiation via calcineurin and Notch signaling
    Atsuko Kasahara
    Department of Cell Physiology and Metabolism, University of Geneva, 1206 Geneva, Switzerland
    Science 342:734-7. 2013
    ..Ablation of mitochondrial fusion proteins Mitofusin 1 and 2 in the embryonic mouse heart, or gene-trapping of Mitofusin 2 or Optic atrophy 1 in mouse embryonic stem cells (ESCs), arrested mouse heart development and impaired ..
  5. pmc Loss of mitofusin 2 promotes endoplasmic reticulum stress
    Gladys A Ngoh
    Whitaker Cardiovascular Institute, Boston University School of Medicine, Boston, Massachusetts 02118, USA
    J Biol Chem 287:20321-32. 2012
    The outer mitochondrial membrane GTPase mitofusin 2 (Mfn2) is known to regulate endoplasmic reticulum (ER) shape in addition to its mitochondrial fusion effects. However, its role in ER stress is unknown...
  6. pmc Mitofusin 2 (Mfn2) links mitochondrial and endoplasmic reticulum function with insulin signaling and is essential for normal glucose homeostasis
    David Sebastian
    Institute for Research in Biomedicine IRB Barcelona, 08028 Barcelona, Spain
    Proc Natl Acad Sci U S A 109:5523-8. 2012
    ..In this connection, mitofusin 2 (Mfn2) participates in mitochondrial fusion and undergoes repression in muscle from obese or type 2 diabetic ..
  7. pmc Mitochondrial fusion is essential for organelle function and cardiac homeostasis
    Yun Chen
    Center for Pharmacogenomics, Department of Internal Medicine, Washington University School of Medicine, St Louis, MO 63110, USA
    Circ Res 109:1327-31. 2011
    ..Mitochondrial fusion has not been observed in postmitotic myocytes of adult hearts, and its occurrence and function in this context are controversial...
  8. pmc Control of mitochondrial morphology through differential interactions of mitochondrial fusion and fission proteins
    Pinwei Huang
    Mitochondrial Research and Innovation Group, Department of Anesthesiology, University of Rochester School of Medicine and Dentistry, Rochester, New York, United States of America
    PLoS ONE 6:e20655. 2011
    ..In this study, we found that two heptad-repeat regions (HR1 and HR2) of Mfn2 interact with each other, and that Mfn2 also interacts with the fission protein DLP1...
  9. pmc Mitofusin-2 maintains mitochondrial structure and contributes to stress-induced permeability transition in cardiac myocytes
    Kyriakos N Papanicolaou
    Molecular Cardiology Whitaker Cardiovascular Institute, Boston University School of Medicine, 715 Albany Street, W611, Boston, MA 02118, USA
    Mol Cell Biol 31:1309-28. 2011
    ..We conclude that in cardiac myocytes, Mfn-2 controls mitochondrial morphogenesis and serves to predispose cells to mitochondrial permeability transition and to trigger cell death...
  10. pmc Mitochondrial fusion is required for mtDNA stability in skeletal muscle and tolerance of mtDNA mutations
    Hsiuchen Chen
    Division of Biology, California Institute of Technology, Pasadena, CA 91125, USA
    Cell 141:280-9. 2010
    ..of mitochondrial fusion in differentiated skeletal muscle through conditional deletion of the mitofusins Mfn1 and Mfn2, mitochondrial GTPases essential for fusion...
  11. pmc Mitofusin 2 is necessary for transport of axonal mitochondria and interacts with the Miro/Milton complex
    Albert Misko
    Department of Neurology and Hope Center for Neurological Diseases, Washington University School of Medicine, St Louis, Missouri 63110, USA
    J Neurosci 30:4232-40. 2010
    Mitofusins (Mfn1 and Mfn2) are outer mitochondrial membrane proteins involved in regulating mitochondrial dynamics...
  12. doi Mitochondrial fission factor Drp1 is essential for embryonic development and synapse formation in mice
    Naotada Ishihara
    Department of Physiology and Cell Biology, Tokyo Medical and Dental University, Tokyo 113 8519, Japan
    Nat Cell Biol 11:958-66. 2009
    ....
  13. pmc Mitofusins and OPA1 mediate sequential steps in mitochondrial membrane fusion
    Zhiyin Song
    Howard Hughes Medical Institute and Division of Biology, California Institute of Technology, Pasadena, CA 91125, USA
    Mol Biol Cell 20:3525-32. 2009
    ..Three large GTPases--OPA1 and the mitofusins Mfn1 and Mfn2--are essential for the fusion of mammalian mitochondria...
  14. pmc SLP-2 is required for stress-induced mitochondrial hyperfusion
    Daniel Tondera
    Department of Cell Biology, University of Geneva, Geneva, Switzerland
    EMBO J 28:1589-600. 2009
    ..Stress-induced mitochondrial hyperfusion (SIMH) is independent of MFN2, BAX/BAK, and prohibitins, but requires L-OPA1, MFN1, and the mitochondrial inner membrane protein SLP-2...
  15. doi Mitofusin 2 tethers endoplasmic reticulum to mitochondria
    Olga Martins de Brito
    Dulbecco Telethon Institute, Venetian Institute of Molecular Medicine, Via Orus 2, 35129 Padova, Italy
    Nature 456:605-10. 2008
    ..Here we show that mitofusin 2, a mitochondrial dynamin-related protein mutated in the inherited motor neuropathy Charcot-Marie-Tooth type IIa,..
  16. pmc Mitochondrial fusion is increased by the nuclear coactivator PGC-1beta
    Marc Liesa
    Institute for Research in Biomedicine IRB Barcelona, Barcelona, Spain
    PLoS ONE 3:e3613. 2008
    ..There is no evidence to date on whether transcriptional regulators are able to shift the balance between mitochondrial fusion and fission events through selective control of gene expression...
  17. ncbi Mitochondrial fusion protects against neurodegeneration in the cerebellum
    Hsiuchen Chen
    Division of Biology, California Institute of Technology, Pasadena, CA 91125, USA
    Cell 130:548-62. 2007
    Mutations in the mitochondrial fusion gene Mfn2 cause the human neurodegenerative disease Charcot-Marie-Tooth type 2A. However, the cellular basis underlying this relationship is poorly understood...
  18. pmc Bak regulates mitochondrial morphology and pathology during apoptosis by interacting with mitofusins
    Craig Brooks
    Department of Cellular Biology and Anatomy, Medical College of Georgia and Veterans Affairs Medical Center, Augusta, GA 30912, USA
    Proc Natl Acad Sci U S A 104:11649-54. 2007
    ..Bak interacts with Mfn1 and Mfn2, two mitochondrial fusion proteins...
  19. ncbi Mitofusin-2 determines mitochondrial network architecture and mitochondrial metabolism. A novel regulatory mechanism altered in obesity
    Daniel Bach
    Parc Cientific de Barcelona, Facultat de Biologia, Universitat de Barcelona, Barcelona 08028, Spain
    J Biol Chem 278:17190-7. 2003
    ..We show that Mfn2 (mitofusin 2), a mitochondrial membrane protein that participates in mitochondrial fusion in mammalian cells, is induced ..
  20. ncbi Structural basis of mitochondrial tethering by mitofusin complexes
    Takumi Koshiba
    Division of Biology, California Institute of Technology, 1200 East California Boulevard, MC114 96, Pasadena, CA 91125, USA
    Science 305:858-62. 2004
    ..Consistent with this proposal, truncated mitofusin, in an HR2-dependent manner, causes mitochondria to become apposed with a uniform gap. Our results suggest that HR2 functions as a mitochondrial tether before fusion...
  21. ncbi Membrane topology and mitochondrial targeting of mitofusins, ubiquitous mammalian homologs of the transmembrane GTPase Fzo
    Manuel Rojo
    INSERM U 523 Institut de Myologie, Groupe Hospitalier Pitie Salpetriere, 47 Boulevard de l Hopital, 75651 Paris Cedex 13, France
    J Cell Sci 115:1663-74. 2002
    Two human Fzo-homologs, mitofusins Mfn1 and Mfn2, are shown by RT-PCR and western blot to be ubiquitous mitochondrial proteins...
  22. pmc Complementation between mouse Mfn1 and Mfn2 protects mitochondrial fusion defects caused by CMT2A disease mutations
    Scott A Detmer
    Division of Biology, California Institute of Technology, Pasadena, CA 91125, USA
    J Cell Biol 176:405-14. 2007
    b>Mfn2, an oligomeric mitochondrial protein important for mitochondrial fusion, is mutated in Charcot-Marie-Tooth disease (CMT) type 2A, a peripheral neuropathy characterized by axonal degeneration...
  23. ncbi Mutational analysis of action of mitochondrial fusion factor mitofusin-2
    Shinji Honda
    Department of Biological Sciences, Tokyo Institute of Technology, 4259 B 19 Nagatsuta cho, Midori ku, Yokohama 226 8501, Japan
    J Cell Sci 118:3153-61. 2005
    Mitofusin-2 (Mfn2) is an essential component of mitochondrial fusion machinery, but its molecular mechanism of action is not clear...
  24. ncbi Disruption of fusion results in mitochondrial heterogeneity and dysfunction
    Hsiuchen Chen
    Division of Biology, California Institute of Technology, Pasadena, California 91125, USA
    J Biol Chem 280:26185-92. 2005
    ..Here, we show that cells with targeted null mutations in Mfn1 or Mfn2 retained low levels of mitochondrial fusion and escaped major cellular dysfunction...
  25. ncbi Role of Bax and Bak in mitochondrial morphogenesis
    Mariusz Karbowski
    Biochemistry Section, SNB, NINDS, NIH, Bethesda, Maryland 20892, USA
    Nature 443:658-62. 2006
    ..Bax seems to induce mitochondrial fusion by activating assembly of the large GTPase Mfn2 and changing its submitochondrial distribution and membrane mobility-properties that correlate with different GTP-..
  26. ncbi Evidence for a mitochondrial regulatory pathway defined by peroxisome proliferator-activated receptor-gamma coactivator-1 alpha, estrogen-related receptor-alpha, and mitofusin 2
    Francesc X Soriano
    Institute for Research in Biomedicine IRB, Scientific Park of Barcelona, Departament of Biochemistry and Molecular Biology, Faculty of Biology, University of Barcelona, Barelona, Spain
    Diabetes 55:1783-91. 2006
    b>Mitofusin 2 (Mfn2) is a mitochondrial membrane protein that participates in mitochondrial fusion and regulates mitochondrial metabolism in mammalian cells...
  27. pmc The soluble form of Bax regulates mitochondrial fusion via MFN2 homotypic complexes
    Suzanne Hoppins
    Department of Molecular and Cellular Biology, University of California, Davis, Davis, CA 95616, USA
    Mol Cell 41:150-60. 2011
    In mammals, fusion of the mitochondrial outer membrane is controlled by two DRPs, MFN1 and MFN2, that function in place of a single outer membrane DRP, Fzo1 in yeast...
  28. doi MicroRNA-106b induces mitochondrial dysfunction and insulin resistance in C2C12 myotubes by targeting mitofusin-2
    Ying Zhang
    Department of Pediatrics, Jinling Hospital, Nanjing University School of Medicine, Nanjing 210002, People s Republic of China
    Mol Cell Endocrinol 381:230-40. 2013
    ..MiR-106b was found to target the 3' untranslated region (3' UTR) of mitofusin-2 (Mfn2) through miR-106b binding sites and to downregulate Mfn2 protein abundance at the post-transcriptional level by ..
  29. pmc Mitofusin 2 maintains haematopoietic stem cells with extensive lymphoid potential
    Larry L Luchsinger
    Columbia Center for Translational Immunology, Columbia University Medical Center, New York, New York 10032, USA
    Nature 529:528-31. 2016
    ..Here we show in mice that the short isoform of a critical regulator of HSCs, Prdm16 (refs 4, 5), induces mitofusin 2 (Mfn2), a protein involved in mitochondrial fusion and in tethering of mitochondria to the endoplasmic ..
  30. doi Mitochondrial toxic effects of Aβ through mitofusins in the early pathogenesis of Alzheimer's disease
    Zhaofei Wu
    State Key Laboratory of Brain and Cognitive Sciences, Institute of Biophysics, Chinese Academy of Sciences, 15 Datun Road, Chaoyang District, Beijing, 100101, China
    Mol Neurobiol 50:986-96. 2014
    ..Significant changes of mitofusin GTPases (Mfn1 and Mfn2) were detected both in the PrP-hAPP/hPS1 brains and SH-SY5Y cells...
  31. pmc A small natural molecule promotes mitochondrial fusion through inhibition of the deubiquitinase USP30
    Wen Yue
    1 Laboratory of Apoptosis and Mitochondrial Biology, The State Key Laboratory of Biomembrane and Membrane Biotechnology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China 2 University of Chinese Academy of Sciences, Beijing 100049, China
    Cell Res 24:482-96. 2014
    ..fusion to restore the mitochondrial network and oxidative respiration in cells that are deficient in either Mfn1 or Mfn2. A mitochondria-localized deubiquitinase USP30 is a target of S3...
  32. pmc HSP72 is a mitochondrial stress sensor critical for Parkin action, oxidative metabolism, and insulin sensitivity in skeletal muscle
    Brian G Drew
    David Geffen School of Medicine, Department of Medicine, Division of Endocrinology, Diabetes and Hypertension, University of California, Los Angeles, Los Angeles, CA
    Diabetes 63:1488-505. 2014
    ..translocates to depolarized mitochondria prior to Parkin recruitment and immunoprecipitates with both Parkin and Mfn2 only after specific mitochondrial insult...
  33. doi Bioenergetic roles of mitochondrial fusion
    Eduardo Silva Ramos
    Max Planck Institute for Biology of Ageing, Joseph Stelzmann Strasse 9b, 50931 Cologne, Germany
    Biochim Biophys Acta 1857:1277-83. 2016
    ..Remarkably, mitofusin 2, in addition to its role in fusion, is important for maintaining coenzyme Q levels and may be an integral ..
  34. pmc Mitofusin 2 Deficiency Affects Energy Metabolism and Mitochondrial Biogenesis in MEF Cells
    Maria Kawalec
    Molecular Biology Unit, Mossakowski Medical Research Centre, PAS, Warsaw, Poland
    PLoS ONE 10:e0134162. 2015
    b>Mitofusin 2 (Mfn2), mitochondrial outer membrane protein which is involved in rearrangement of these organelles, was first described in pathology of hypertension and diabetes, and more recently much attention is paid to its functions in ..
  35. pmc Conditional knockout of proximal tubule mitofusin 2 accelerates recovery and improves survival after renal ischemia
    Jonathan M Gall
    Renal Section and
    J Am Soc Nephrol 26:1092-102. 2015
    ..Elimination of the mitochondrial fusion protein mitofusin 2 (Mfn2) sensitizes PT cells to apoptosis in vitro...
  36. pmc A Mitofusin-2-dependent inactivating cleavage of Opa1 links changes in mitochondria cristae and ER contacts in the postprandial liver
    Aditi Sood
    Department of Molecular Biology, Medical Biochemistry and Pathology, Universite Laval, Quebec, Canada G1V 0A6 Mitochondria Biology Laboratory, Centre de Recherche de l Institut Universitaire en Santé Mentale de Québec, Quebec City, QC, Canada G1J 2G3
    Proc Natl Acad Sci U S A 111:16017-22. 2014
    ..However, C-cleavage requires Mitofusin-2 (Mfn2), a key factor in mitochondria-ER tethering, thereby linking cristae remodeling to MERC assembly...
  37. doi Mitoguardin Regulates Mitochondrial Fusion through MitoPLD and Is Required for Neuronal Homeostasis
    Yongping Zhang
    Life Sciences Institute and Innovation Center for Cell Signaling Network, Zhejiang University, Hangzhou 310058, China
    Mol Cell 61:111-24. 2016
    ..Therefore, we propose that MIGA proteins promote mitochondrial fusion by regulating mitochondrial phospholipid metabolism via MitoPLD. ..
  38. doi Loss of mitofusin 2 links beta-amyloid-mediated mitochondrial fragmentation and Cdk5-induced oxidative stress in neuron cells
    Junghyung Park
    School of Life Sciences, BK21 Plus KNU Creative BioResearch Group, Kyungpook National University, Daegu, Korea
    J Neurochem 132:687-702. 2015
    ..ATP, adenosine triphosphate; Bax, Bcl-2-associated X protein; Bcl-2, B-cell lymphoma 2; Cdk5, Cyclin-dependent kinase; Cyt C, cytochrome C; Mfn2, mitofusin 2; Prx2, peroxiredoxin 2; ROS, reactive oxygen species.
  39. pmc The mitochondrial fusion-related proteins Mfn2 and OPA1 are transcriptionally induced during differentiation of bone marrow progenitors to immature dendritic cells
    Seung Wook Ryu
    Department of Bio and Brain Engineering, Korea Advanced Institute of Science and Technology, Daejeon 305 701, Korea KI for the BioCentury, Korea Advanced Institute of Science and Technology, Daejeon 305 701, Korea
    Mol Cells 38:89-94. 2015
    ..b>Mfn2 and OPA1, but not Mfn1, are transcriptionally upregulated during differentiation; however, knockdown of Mfn2 and ..
  40. pmc MFN2 couples glutamate excitotoxicity and mitochondrial dysfunction in motor neurons
    Wenzhang Wang
    From the Department of Pathology and
    J Biol Chem 290:168-82. 2015
    ..in response to glutamate results in the degradation of a key mitochondrial outer membrane fusion regulator, mitofusin 2 (MFN2), and leads to MFN2-mediated mitochondrial fragmentation preceding glutamate-induced neuronal death...
  41. pmc Role of Mitofusin-2 in mitochondrial localization and calcium uptake in skeletal muscle
    Alina Ainbinder
    University of Rochester School of Medicine and Dentistry, Department of Pharmacology and Physiology, Rochester, NY 14642, United States Electronic address
    Cell Calcium 57:14-24. 2015
    ..Mitofusin-2 (Mfn2) is a transmembrane GTPase present in both mitochondria and ER/SR membranes that forms trans-dimers and ..
  42. pmc Murine Mesenchymal Stem Cell Commitment to Differentiation Is Regulated by Mitochondrial Dynamics
    Maria Fernanda Forni
    Departamento de Bioquimica, Instituto de Quimica, Universidade de Sao Paulo, Brazil
    Stem Cells 34:743-55. 2016
    ..Moreover, knockdown of Mfn2 in adipo and osteogenesis and the overexpression of a dominant negative form of Drp1 during chondrogenesis resulted ..
  43. ncbi Mitofusin 2 expression dominates over mitofusin 1 exclusively in mouse dorsal root ganglia - a possible explanation for peripheral nervous system involvement in Charcot-Marie-Tooth 2A
    Maria Kawalec
    Małgorzata Beręsewicz, PhD, Molecular Biology Unit, Mossakowski Medical Research Centre, Polish Academy of Sciences, Warsaw, Poland, E mail
    Folia Neuropathol 52:436-42. 2014
    b>Mitofusin 2 (Mfn2), a protein of the mitochondrial outer membrane, is essential for mitochondrial fusion and contributes to the maintenance and operation of the mitochondrial network...
  44. pmc Mitochondrial Dynamics is a Distinguishing Feature of Skeletal Muscle Fiber Types and Regulates Organellar Compartmentalization
    Prashant Mishra
    Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA 91125, USA
    Cell Metab 22:1033-44. 2015
    ..contain elongated mitochondrial networks with higher fusion rates that are dependent on the mitofusins Mfn1 and Mfn2. Switching of a glycolytic fiber to an oxidative IIA type is associated with elongation of mitochondria, suggesting ..
  45. pmc Mitofusin 2 is required to maintain mitochondrial coenzyme Q levels
    Arnaud Mourier
    Max Planck Institute for Biology of Ageing, 50931 Cologne, Germany
    J Cell Biol 208:429-42. 2015
    ..Despite the established role of mitofusins (MFN1 and MFN2) in mitochondrial fusion, only MFN2 has been associated with metabolic and neurodegenerative diseases, which ..
  46. pmc Mitofusin 2 ablation increases endoplasmic reticulum-mitochondria coupling
    Riccardo Filadi
    Department of Biomedical Sciences, University of Padua, Padua, 35121, Italy
    Proc Natl Acad Sci U S A 112:E2174-81. 2015
    ..Among them, in mammalian cells, mitofusin 2 (Mfn2), located on both the outer mitochondrial membrane and the ER surface, has been proposed to be a physical ..
  47. pmc Sirtuin 1 suppresses mitochondrial dysfunction of ischemic mouse livers in a mitofusin 2-dependent manner
    T G Biel
    Department of Surgery, University of Florida, Gainesville, FL, USA
    Cell Death Differ 23:279-90. 2016
    ..Biochemical approaches revealed that SIRT1 interacts with mitofusin-2 (MFN2). Furthermore, MFN2, but not MFN1, was deacetylated by SIRT1...
  48. pmc Bax regulates primary necrosis through mitochondrial dynamics
    Russell S Whelan
    Department of Medicine, Albert Einstein College of Medicine, Bronx, NY 10461, USA
    Proc Natl Acad Sci U S A 109:6566-71. 2012
    ..Cells lacking mitofusin 2 (Mfn2), which exhibit similar fusion defects, are protected to the same extent as Bax/Bak-null cells...
  49. pmc Mitochondrial dynamics controlled by mitofusins regulate Agrp neuronal activity and diet-induced obesity
    Marcelo O Dietrich
    Program in Integrative Cell Signaling and Neurobiology of Metabolism, Section of Comparative Medicine, Yale University School of Medicine, New Haven, CT 06520, USA Department of Biochemistry, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS 90035, Brazil Electronic address
    Cell 155:188-99. 2013
    ..with mitochondrial fusion mechanisms in Agrp neurons by cell-selectively knocking down mitofusin 1 (Mfn1) or mitofusin 2 (Mfn2) resulted in altered mitochondria size and density in these cells...
  50. doi Mitofusin 2 is necessary for striatal axonal projections of midbrain dopamine neurons
    Seungmin Lee
    Department of Laboratory Medicine, and 2Department of Neuroscience, Karolinska Institutet, Retzius vag 8, Stockholm, Sweden
    Hum Mol Genet 21:4827-35. 2012
    ..the E3 ubiquitin ligase Parkin has been shown to directly regulate the levels of mitofusin 1 (Mfn1) and Mfn2, two homologous outer membrane large GTPases that govern mitochondrial fusion, but it is not known whether this is ..
  51. doi Liver-specific reduction of Mfn2 protein by RNAi results in impaired glycometabolism and lipid homeostasis in BALB/c mice
    Xiaolin Chen
    Department of Endocrinology, Renmin Hospital of Wuhan University, Wuhan 430060, China
    J Huazhong Univ Sci Technolog Med Sci 29:689-96. 2009
    Mitofusin-2 (Mfn2) gene expression is positively correlated with insulin sensitivity in patients with type 2 diabetes. However, it is unclear if Mfn2 is involved in carbohydrate metabolism and lipid homeostasis...
  52. doi Mitochondrial membrane potential is required for MAVS-mediated antiviral signaling
    Takumi Koshiba
    1Department of Biology, Faculty of Sciences, Kyushu University, 6 10 1 Hakozaki, Higashi ku, Fukuoka 812 8581, Japan
    Sci Signal 4:ra7. 2011
    ..the ability to undergo mitochondrial fusion as a result of targeted deletion of both mitofusin 1 (Mfn1) and mitofusin 2 (Mfn2) exhibited impaired induction of interferons and proinflammatory cytokines in response to viral infection,..
  53. pmc Role of mitofusin 2 in the renal stress response
    Jonathan M Gall
    Renal Section, Boston Medical Center, Boston, Massachusetts, United States of America
    PLoS ONE 7:e31074. 2012
    The role of mitofusin 2 (MFN2), a key regulator of mitochondrial morphology and function in the renal stress response is unknown...
  54. pmc Lysocardiolipin acyltransferase 1 (ALCAT1) controls mitochondrial DNA fidelity and biogenesis through modulation of MFN2 expression
    Jia Li
    Shaanxi Center for Stem Cell Engineering and Technology, Northwest A and F University, Yangling, Shaanxi 712100, China
    Proc Natl Acad Sci U S A 109:6975-80. 2012
    ..overexpression of ALCAT1 causes mitochondrial fragmentation through oxidative stress and depletion of mitofusin mitofusin 2 (MFN2) expression...
  55. doi Up-regulation of mitofusin-2 protects CD4+ T cells from HMGB1-mediated immune dysfunction partly through Ca(2+)-NFAT signaling pathway
    Guang ju Zhao
    Emergency Department, The First Affiliated Hospital of Wenzhou Medical College, Wenzhou 325000, PR China
    Cytokine 59:79-85. 2012
    ..We found that the expression of mitofusin-2 (Mfn2; also named hyperplasia suppressor gene), a member of the mitofusin family, was decreased in CD4(+) T lymphocytes ..
  56. pmc Loss of Mfn2 results in progressive, retrograde degeneration of dopaminergic neurons in the nigrostriatal circuit
    Anh H Pham
    Division of Biology, California Institute of Technology, 1200 E California Boulevard, Pasadena, CA 91125, USA
    Hum Mol Genet 21:4817-26. 2012
    ..Because the mitofusins Mfn1 and Mfn2 are essential for mitochondrial fusion, we deleted these genes from a subset of dopaminergic neurons in mice...
  57. pmc Mitofusins 1 and 2 are essential for postnatal metabolic remodeling in heart
    Kyriakos N Papanicolaou
    Whitaker Cardiovascular Institute, Boston University School of Medicine, Boston, MA, USA
    Circ Res 111:1012-26. 2012
    ..Mitofusins (Mfn-1 and Mfn-2) are known regulators of mitochondrial networks, but their role during perinatal maturation of the heart has yet to be examined...
  58. pmc Two rare human mitofusin 2 mutations alter mitochondrial dynamics and induce retinal and cardiac pathology in Drosophila
    William H Eschenbacher
    Center for Pharmacogenomics, Department of Internal Medicine, Washington University School of Medicine, St Louis, Missouri, United States of America
    PLoS ONE 7:e44296. 2012
    ..Inexplicably, loss of function mutations of mitofusin 2 (Mfn2) specifically affect neurological tissue, causing Charcot Marie Tooth syndrome (CMT) and atypical optic ..
  59. pmc Mitofusin-2 independent juxtaposition of endoplasmic reticulum and mitochondria: an ultrastructural study
    Pierre Cosson
    Department for Cell Physiology and Metabolism, Centre Medical Universitaire, Geneva Faculty of Medicine, Geneva, Switzerland
    PLoS ONE 7:e46293. 2012
    ....
  60. doi MITOL regulates endoplasmic reticulum-mitochondria contacts via Mitofusin2
    Ayumu Sugiura
    Laboratory of Molecular Biochemistry, School of Life Sciences, Tokyo University of Pharmacy and Life Sciences, Hachioji, Tokyo 192 0392, Japan
    Mol Cell 51:20-34. 2013
    ..regulates mitochondria-associated endoplasmic reticulum (ER) membrane (MAM) domain formation through mitofusin2 (Mfn2). MITOL interacts with and ubiquitinates mitochondrial Mfn2, but not ER-associated Mfn2...
  61. pmc PINK1-phosphorylated mitofusin 2 is a Parkin receptor for culling damaged mitochondria
    Yun Chen
    Center for Pharmacogenomics, Department of Internal Medicine, Washington University School of Medicine, St Louis, MO 63110, USA
    Science 340:471-5. 2013
    ..Parkin bound to Mfn2 in a PINK1-dependent manner; PINK1 phosphorylated Mfn2 and promoted its Parkin-mediated ubiqitination...
  62. pmc Mfn2 modulates the UPR and mitochondrial function via repression of PERK
    Juan Pablo Munoz
    Institute for Research in Biomedicine IRB Barcelona, Barcelona, Spain
    EMBO J 32:2348-61. 2013
    b>Mitofusin 2 (Mfn2) is a key protein in mitochondrial fusion and it participates in the bridging of mitochondria to the endoplasmic reticulum (ER). Recent data indicate that Mfn2 ablation leads to ER stress...
  63. pmc Central role of mitofusin 2 in autophagosome-lysosome fusion in cardiomyocytes
    Ting Zhao
    Institute of Molecular Medicine, State Key Laboratory of Biomembrane and Membrane Biotechnology, Peking Tsinghua Center for Life Sciences, Peking University, Beijing 100871, China
    J Biol Chem 287:23615-25. 2012
    ..We previously reported that mitofusin 2 (MFN2), a mitochondrial outer membrane protein, serves as a major determinant of cardiomyocyte apoptosis ..
  64. ncbi Dysregulation of HSG triggers vascular proliferative disorders
    Kuang Hueih Chen
    The Institute of Cardiovascular Science and The Institute of Molecular Medicine, Peking University, Beijing 100083, China
    Nat Cell Biol 6:872-83. 2004
    ..Thus, rHSG functions as a cell proliferation suppressor, whereas dysregulation of rHSG results in proliferative disorders...
  65. ncbi Expression of HSG is essential for mouse blastocyst formation
    Guang Jian Jiang
    Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing 100080, China
    Biochem Biophys Res Commun 335:351-5. 2005
    ..When mouse zygotes were injected with HSG antisense plasmid and cultured in vitro, their capacity to form blastocysts was severely impaired. Our results indicate that HSG plays an essential role in mouse preimplantation development...
  66. ncbi Genetic and phenotypic analysis of Tcm, a mutation affecting early eye development
    Ken S Wang
    F M Kirby Center for Molecular Ophthalmology, Scheie Eye Institute, University of Pennsylvania School of Medicine, Stellar Chance Bldg Rm 315, 422 Curie Blvd, Philadelphia, Pennsylvania 19104, USA
    Mamm Genome 16:332-43. 2005
    ..These results indicate that the causitive Tcm mutation falls within a noncoding regulatory region of one of the five candidate genes or in an undescribed gene...
  67. ncbi Mitofusin 2 (Mfn2): a key player in insulin-dependent myogenesis in vitro
    Patrycja Pawlikowska
    Department of Physiological Sciences, Faculty of Veterinary Medicine, Warsaw Agricultural University, Nowoursynowska 159, 02 776 Warsaw, Poland
    Cell Tissue Res 327:571-81. 2007
    ..Our present study focuses on the mitochondrial transmembrane protein, hyperplasia suppressor gene/mitofusin2 (HSG/Mfn2), which regulates both mitochondrial fusion (as demonstrated by perinuclear mitochondria clustering) and insulin-..
  68. ncbi Down-regulation of mitofusin-2 expression in cardiac hypertrophy in vitro and in vivo
    Lu Fang
    Baker Heart Research Institute and Alfred Heart Centre, Alfred Hospital, Melbourne, Australia
    Life Sci 80:2154-60. 2007
    Mitofusin-2 (Mfn2) suppresses smooth muscle cell proliferation through inhibition of the Ras-extracellular signal-regulated kinases (ERK1/2) pathway...
  69. pmc Genome-wide analysis of the H3K4 histone demethylase RBP2 reveals a transcriptional program controlling differentiation
    Nuria Lopez-Bigas
    Research Unit on Biomedical Informatics, Experimental and Health Science Department, Universitat Pompeu Fabra, Barcelona 08080, Spain
    Mol Cell 31:520-30. 2008
    ..We conclude that, during differentiation, RBP2 exerts inhibitory effects on multiple genes through direct interaction with their promoters...
  70. pmc IL-6 protects against hyperoxia-induced mitochondrial damage via Bcl-2-induced Bak interactions with mitofusins
    Aaron B Waxman
    Pulmonary Critical Care Unit, Department of Medicine, Massachusetts General Hospital, Harvard Medical School, 55 Fruit Street, Bulfinch 148, Boston, MA 02114, USA
    Am J Respir Cell Mol Biol 41:385-96. 2009
    ..Taken together, our results suggest that IL-6 induces Bcl-2 expression to perform cytoprotective functions in response to oxygen toxicity, and that this effect is mediated by alterations in the interactions between Bak and Mfns...
  71. pmc Peroxisome proliferator-activated receptor delta regulates mitofusin 2 expression in the heart
    Yuquan Li
    Department of Nutrition Sciences, University of Alabama at Birmingham, Birmingham, AL 35294 3360, USA
    J Mol Cell Cardiol 46:876-82. 2009
    b>Mitofusin 2 (Mfn2) has been proposed as an important mitochondrial protein in maintaining mitochondrial network and bioenergetics. Mfn2 is highly expressed in the heart, but is downregulated in response to hypertrophic stimuli...
  72. doi Mitofusin-2 regulates mitochondrial and endoplasmic reticulum morphology and tethering: the role of Ras
    Olga Martins de Brito
    Dulbecco Telethon Institute, Venetian Institute of Molecular Medicine, Via Orus 2, 35129 Padova, Italy
    Mitochondrion 9:222-6. 2009
    ..b>MFN2 also binds and inhibits the proto-oncogene Ras that controls proliferation, cell cycle and morphology...
  73. pmc Drp1 levels constitutively regulate mitochondrial dynamics and cell survival in cortical neurons
    Takuma Uo
    Department of Neurological Surgery, University of Washington School of Medicine, Seattle, 98195 6470, USA
    Exp Neurol 218:274-85. 2009
    ..Conversely, depletion of the fusion protein, Mfn2, but not Mfn1, caused extensive mitochondrial fission and cell death...
  74. doi Mitofusin 2 inhibits mitochondrial antiviral signaling
    Kai Yasukawa
    Department of Biology, Kyushu University, Hakozaki, Higashi ku, Fukuoka, Japan
    Sci Signal 2:ra47. 2009
    ..Here, we report that mitofusin 2 (Mfn2), a mediator of mitochondrial fusion, interacts with MAVS to modulate antiviral immunity...
  75. pmc Fragmented mitochondria are sensitized to Bax insertion and activation during apoptosis
    Craig Brooks
    Dept of Cellular Biology and Anatomy, Medical College of Georgia, 1459 Laney Walker Blvd, Augusta, GA 30912, USA
    Am J Physiol Cell Physiol 300:C447-55. 2011
    ..Mechanistically, mitochondrial fragmentation may sensitize the cells to Bax insertion and activation in mitochondria, facilitating the release of apoptogenic factors and consequent apoptosis...
  76. pmc Mitofusin 2 regulates STIM1 migration from the Ca2+ store to the plasma membrane in cells with depolarized mitochondria
    Karthika Singaravelu
    Department of Physiology, Anatomy, and Genetics, University of Oxford, Sherrington Building, Parks Road, Oxford OX1 3PT, United Kingdom
    J Biol Chem 286:12189-201. 2011
    ..We identify the dynamin-related mitochondrial protein mitofusin 2, mutations of which causes the inherited neurodegenerative disease Charcot-Marie-Tooth IIa in humans, as an ..
  77. doi Bioenergetic defect associated with mKATP channel opening in a mouse model carrying a mitofusin 2 mutation
    Virginie Guillet
    Unité Mixte de Recherche Centre National de Recherche Scientifique CNRS 6214, Institut National de Santé et de Recherche Me dicale INSERM U771, Angers, France
    FASEB J 25:1618-27. 2011
    ..type 2A (CMT2A) is an autosomal dominant axonal form of peripheral neuropathy caused by mutations in the mitofusin 2 gene (MFN2), which encodes a mitochondrial outer membrane protein that promotes mitochondrial fusion...
  78. doi Expression of nuclear-encoded genes involved in mitochondrial biogenesis and dynamics in experimentally denervated muscle
    Akira Wagatsuma
    Graduate School of Arts and Sciences, The University of Tokyo, Tokyo, Japan
    J Physiol Biochem 67:359-70. 2011
    ..proliferator-activated receptor, γ coactivator 1 (PGC-1)α, estrogen-related receptor α (ERRα), and mitofusin 2 were down-regulated throughout the experimental period, whereas those of PGC-1β, PRC, nuclear respiratory ..

Research Grants3

  1. Il-6 type cytokine protection from hyperoxic lung injury
    Aaron Waxman; Fiscal Year: 2007
    ..abstract_text> ..
  2. PHOSPHOLIPASE C AND CARDIAC HYPERTROPHY
    GERALD DORN; Fiscal Year: 2005
    ..abstract_text> ..
  3. Calpains as Mediators of Cardiac Ischemic Injury
    Gerald W Dorn; Fiscal Year: 2010
    ..Collectively, these studies will apply state-of-the-art techniques for in vivo genetic manipulation, microphysiologic analysis, and biochemical assessment to achieve insight into the roles of myocardial calpains in health and disease. ..