The Soluble Form of Bax Regulates Mitochondrial Fusion via MFN2 Homotypic Complexes

被引:196
作者
Hoppins, Suzanne [1 ]
Edlich, Frank [2 ]
Cleland, Megan M. [2 ]
Banerjee, Soojay [2 ]
McCaffery, J. Michael [3 ]
Youle, Richard J. [2 ]
Nunnari, Jodi [1 ]
机构
[1] Univ Calif Davis, Dept Mol & Cellular Biol, Davis, CA 95616 USA
[2] NINDS, Surg Neurol Branch, Bethesda, MD 20892 USA
[3] Johns Hopkins Univ, Integrated Imaging Ctr, Baltimore, MD 21218 USA
关键词
M-AAA PROTEASE; MITOFUSIN; 2; MAMMALIAN-CELLS; IN-VITRO; OPA1; APOPTOSIS; DYNAMICS; FISSION; ACTIVATION; MUTATIONS;
D O I
10.1016/j.molcel.2010.11.030
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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.
引用
收藏
页码:150 / 160
页数:11
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