膜去极化通过刺激自身切割激活线粒体蛋白酶 OMA1。
Membrane depolarization activates the mitochondrial protease OMA1 by stimulating self-cleavage.
机构信息
College of Life Sciences, Wuhan University, Wuhan, China.
出版信息
EMBO Rep. 2014 May;15(5):576-85. doi: 10.1002/embr.201338240. Epub 2014 Apr 9.
Abstract
Mitochondrial inner membrane fusion depends on the dynamin-related GTPase OPA1 and the function of OPA1 is regulated by proteolytic cleavage. The mitochondrial proteases Yme1L and OMA1 cleave OPA1 at S2 and S1 sites, respectively. Here, we show that OMA1 is cleaved to a short form (S-OMA1) by itself upon mitochondrial membrane depolarization; S-OMA1 is degraded quickly but could be stabilized by CCCP treatment or Prohibitin knockdown in cells. In addition, OMA1 processing is positively correlated with OPA1 cleavage at the S1 site and the regulation of mitochondrial morphology. Thus, our results reveal the molecular mechanism for OMA1 activation toward OPA1 processing.
摘要
线粒体内膜融合依赖于与 dynamin 相关的 GTP 酶 OPA1，OPA1 的功能受蛋白水解切割的调节。线粒体蛋白酶 Yme1L 和 OMA1 分别在 S2 和 S1 位点切割 OPA1。在这里，我们表明 OMA1 在线粒体膜去极化时自身被切割成短形式（S-OMA1）；S-OMA1 迅速降解，但在细胞中用 CCCP 处理或抑制 Prohibitin 表达可稳定 S-OMA1。此外，OMA1 加工与 S1 位点的 OPA1 切割和线粒体形态的调节呈正相关。因此，我们的结果揭示了 OMA1 对 OPA1 加工的激活的分子机制。
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