Oma1, a novel membrane-bound metallopeptidase in mitochondria with activities overlapping with the m-AAA protease
Oma1, a novel membrane-bound metallopeptidase in mitochondria with activities overlapping with the m-AAA protease
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DOI：
10.1074/jbc.m305584200
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发表时间：
2003-11-21
影响因子：
4.8
通讯作者：
Langer, T
中科院分区：
文献类型：
--
作者：
Käser, M;Kambacheld, M;Langer, T
线粒体内膜的完整性由膜包埋质量控制系统维持，该系统确保错误折叠的膜蛋白的去除。两个ATP依赖性AAA蛋白酶的催化位点在相反的膜表面是这个蛋白水解系统的关键组成部分。在这里，我们描述了一种新的保守的金属肽酶，发挥活动重叠的m-AAA蛋白酶，因此被称为奥马1的鉴定。这两种肽酶都是内膜的组成部分，并介导多面体内膜蛋白Oxa 1的错误折叠衍生物的蛋白水解分解。m-AAA蛋白酶切割掉Oxa 1的暴露于基质的C-末端结构域，并降解其跨膜结构域。在没有m-AAA蛋白酶的情况下，Oxa 1的蛋白水解以ATP非依赖性方式由Oma 1和一种未知的肽酶介导，导致N-和C-末端蛋白水解片段的积累。Oma 1暴露其蛋白水解中心的基质侧，然而，映射Oma 1切割位点揭示了Oxa 1在两个膜表面的环区域的剪切。这些结果确定Oma 1作为线粒体内膜中质量控制系统的新组分。与Oma 1同源的蛋白质存在于高等真核细胞、真细菌和古细菌中，表明Oma 1是膜包埋金属肽酶保守家族的创始成员。
The integrity of the inner membrane of mitochondria is maintained by a membrane-embedded quality control system that ensures the removal of misfolded membrane proteins. Two ATP-dependent AAA proteases with catalytic sites at opposite membrane surfaces are key components of this proteolytic system. Here we describe the identification of a novel conserved metallopeptidase that exerts activities overlapping with the m-AAA protease and was therefore termed Oma1. Both peptidases are integral parts of the inner membrane and mediate the proteolytic breakdown of a misfolded derivative of the polytopic inner membrane protein Oxa1. The m-AAA protease cleaves off the matrix-exposed C-terminal domain of Oxa1 and processively degrades its transmembrane domain. In the absence of the m-AAA protease, proteolysis of Oxa1 is mediated in an ATP-independent manner by Oma1 and a yet unknown peptidase resulting in the accumulation of N- and C-terminal proteolytic fragments. Oma1 exposes its proteolytic center to the matrix side; however, mapping of Oma1 cleavage sites reveals clipping of Oxa1 in loop regions at both membrane surfaces. These results identify Oma1 as a novel component of the quality control system in the inner membrane of mitochondria. Proteins homologous to Oma1 are present in higher eukaryotic cells, eubacteria and archaebacteria, suggesting that Oma1 is the founding member of a conserved family of membrane-embedded metallopeptidases.