MARCH-V is a novel mitofusin 2- and Drp1-binding protein able to change mitochondrial morphology.
Mitofusins and Drp1 are key components in mitochondrial membrane fusion and division, but the molecular mechanism underlying the regulation of their activities remains to be clarified. Here, we identified human membrane-associated RING-CH (MARCH)-V as a novel transmembrane protein of the mitochondrial outer membrane. Immunoprecipitation studies demonstrated that MARCH-V interacts with mitofusin 2 (MFN2) and ubiquitinated forms of Drp1. Overexpression of MARCH-V promoted the formation of long tubular mitochondria in a manner that depends on MFN2 activity. By contrast, mutations in the RING finger caused fragmentation of mitochondria. We also show that MARCH-V promotes ubiquitination of Drp1. These results indicate that MARCH-V has a crucial role in the control of mitochondrial morphology by regulating MFN2 and Drp1 activities.
Nakamura
Nobuhiro
N
Department of Biological Sciences, Tokyo Institute of Technology, 4259-B19 Nagatsuta-cho, Midori-ku, Yokohama, 226-8501, Japan.
Kimura
Yasuo
Y
Tokuda
Masaki
M
Honda
Shinji
S
Hirose
Shigehisa
S
D000818:Animals; D019556:COS Cells; D002352:Carrier Proteins / Q000235:genetics; D002522:Chlorocebus aethiops; D034281:Dynamins; D020558:GTP Phosphohydrolases / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D008869:Microtubule-Associated Proteins / Q000378:metabolism*; D008928:Mitochondria / Q000502:physiology*; D051336:Mitochondrial Membranes / Q000378:metabolism / Q000502:physiology; D024101:Mitochondrial Proteins / Q000378:metabolism*; D011485:Protein Binding; D012689:Sequence Homology, Nucleic Acid; D014162:Transfection; D025801:Ubiquitin / Q000378:metabolism; D044767:Ubiquitin-Protein Ligases / Q000378:metabolism* / Q000502:physiology*
D002352:Carrier Proteins; D008565:Membrane Proteins; D008869:Microtubule-Associated Proteins; D024101:Mitochondrial Proteins; D025801:Ubiquitin; C502926:MARCHF2 protein, human; C515578:MARCHF5 protein, human; D044767:Ubiquitin-Protein Ligases; D020558:GTP Phosphohydrolases; C470018:MFN2 protein, human; C110768:DNM1L protein, human; D034281:Dynamins