The soluble form of Bax regulates mitochondrial fusion via MFN2 homotypic complexes.
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. We addressed the significance of two mammalian outer membrane fusion DRPs using an in vitro mammalian mitochondrial fusion assay. We demonstrate that heterotypic MFN1-MFN2 trans complexes possess greater efficacy in fusion as compared to homotypic MFN1 or MFN2 complexes. In addition, we show that the soluble form of the proapoptotic Bcl2 protein, Bax, positively regulates mitochondrial fusion exclusively through homotypic MFN2 trans complexes. Together, these data demonstrate functional and regulatory distinctions between MFN1 and MFN2 and provide insight into their unique physiological roles.
Department of Molecular and Cellular Biology, University of California, Davis, Davis, CA 95616, USA.
Suzanne
S
Hoppins
Frank
F
Edlich
Megan M
MM
Cleland
Soojay
S
Banerjee
J Michael
JM
McCaffery
Richard J
RJ
Youle
Jodi
J
Nunnari
D000818:Animals; D002478:Cells, Cultured; D020558:GTP Phosphohydrolases / Q000378:metabolism*; D051379:Mice; D008928:Mitochondria / Q000378:metabolism* / Q000648:ultrastructure; D051336:Mitochondrial Membranes / Q000378:metabolism; D024101:Mitochondrial Proteins / Q000737:chemistry / Q000378:metabolism / Q000502:physiology*; D012995:Solubility; D051028:bcl-2-Associated X Protein / Q000737:chemistry / Q000502:physiology*
C494827:Bax protein, mouse; D024101:Mitochondrial Proteins; D051028:bcl-2-Associated X Protein; D020558:GTP Phosphohydrolases; C488751:Mfn2 protein, mouse
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