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The soluble form of Bax regulates mitochondrial fusion via MFN2 homotypic complexes.

ABSTRACT: 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.

SUBMITTER: Hoppins S

PROVIDER: S-EPMC3072068 | biostudies-literature | 2011 Jan

REPOSITORIES: biostudies-literature

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The soluble form of Bax regulates mitochondrial fusion via MFN2 homotypic complexes.

Hoppins Suzanne S Edlich Frank F Cleland Megan M MM Banerjee Soojay S McCaffery J Michael JM Youle Richard J RJ Nunnari Jodi J

Molecular cell 20110101 2

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 proapoptoti ...[more]

PMID: 21255726

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MTCH2 cooperates with MFN2 and lysophosphatidic acid synthesis to sustain mitochondrial fusion

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Mitofusins Mfn1 and Mfn2 coordinately regulate mitochondrial fusion and are essential for embryonic development.

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