The mitochondrial fission receptor Mff selectively recruits oligomerized Drp1.
The mitochondrial fission receptor Mff selectively recruits oligomerized Drp1.
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DOI：
10.1091/mbc.e15-08-0591
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发表时间：
2015-12-01
影响因子：
3.3
通讯作者：
Chan DC
中科院分区：
文献类型：
--
作者：
Liu R;Chan DC
The GTPase Drp1 is recruited to mitochondria by outer membrane receptors to drive mitochondrial fission. The receptor Mff selectively binds to oligomerized Drp1, in contrast to the alternative receptors MiD51 and MiD49. These results show that Drp1 receptors recruit different subpopulations of Drp1 and may explain their distinct biological effects. Dynamin-related protein 1 (Drp1) is the GTP-hydrolyzing mechanoenzyme that catalyzes mitochondrial fission in the cell. Residing in the cytosol as dimers and tetramers, Drp1 is recruited by receptors on the mitochondrial outer membrane, where it further assembles into a helical ring that drives division via GTP-dependent constriction. The Drp1 receptor Mff is a major regulator of mitochondrial fission, and its overexpression results in increased fission. In contrast, the alternative Drp1 receptors MiD51 and MiD49 appear to recruit inactive forms of Drp1, because their overexpression inhibits fission. Using genetic and biochemical assays, we studied the interaction of Drp1 with Mff. We show that the insert B region of Drp1 inhibits Mff–Drp1 interactions, such that recombinant Drp1 mutants lacking insert B form a stable complex with Mff. Mff cannot bind to assembly-deficient mutants of Drp1, suggesting that Mff selectively interacts with higher-order complexes of Drp1. In contrast, the alternative Drp1 receptors MiD51 and MiD49 can recruit Drp1 dimers. Therefore Drp1 recruitment by Mff versus MiD51 and MiD49 may result in different outcomes because they recruit different subpopulations of Drp1 from the cytosol.
