The formation of respiratory chain complexes in mitochondria is under the proteolytic control of the m-AAA protease
The formation of respiratory chain complexes in mitochondria is under the proteolytic control of the m-AAA protease
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DOI：
10.1093/emboj/17.16.4837
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发表时间：
1998-08-17
期刊：
影响因子：
11.4
通讯作者：
Langer, T
中科院分区：
文献类型：
--
作者：
Arlt, H;Steglich, G;Langer, T
Yta10p (Afg3p) 和 Yta12p (Rcal1p) 是 ATP 酶保守 AAA 家族的成员，是线粒体 m-AAA 蛋白酶（一种内膜 ATP 依赖性金属肽酶）的成员。 YTA10 或 YTA12 的缺失会损害未组装内膜蛋白的降解和呼吸链复合物的组装。YTA10 或 YTA12 中蛋白水解位点的突变已被证明会抑制膜整合多肽的蛋白水解，但不会抑制细胞的呼吸能力，这表明 Yta10p 和 Yta12p 具有额外的活性。在这里，我们展示了 m-AAA 蛋白酶在呼吸链生物发生中的重要蛋白水解功能。含有蛋白水解失活形式的 Yta10p 和 Yta12p 的细胞具有呼吸缺陷，并表现出与 Delta yta10 和 Delta yta12 细胞相似的多效性表型，它们显示出含内含子的线粒体基因 COX1 和 COB 的表达缺陷，在缺乏 m-AAA 蛋白酶的线粒体中，COX1 和 COB 转录物的剪接受到损害，而转录和翻译可以在如果缺少 Yta10p 或 Yta12p，m-AAA 蛋白酶的功能似乎仅限于编码 mRNA 成熟酶的内含子。我们的结果揭示了 m-AAA 蛋白酶亚基的重叠底物特异性，并解释了缺乏 m-AAA 蛋白酶的线粒体中含内含子基因表达缺陷导致的呼吸链复合物组装受损。
Yta10p (Afg3p) and Yta12p (Rcal1p), members of the conserved AAA family of ATPases, are submits of the mitochondrial m-AAA protease, an inner membrane ATP-dependent metallopeptidase. Deletion of YTA10 or YTA12 impairs degradation of nonassembled inner membrane proteins and assembly of respiratory chain complexes, Mutations of the proteolytic sites in either YTA10 or YTA12 have been shown to inhibit proteolysis of membrane-integrated polypeptides but not the respiratory competence of the cells, suggesting additional activities of Yta10p and Yta12p. Here we demonstrate essential proteolytic functions of the m-AAA protease in the biogenesis of the respiratory chain. Cells harbouring proteolytically inactive forms of both Yta10p and Yta12p are respiratory deficient and exhibit a pleiotropic phenotype similar to Delta yta10 and Delta yta12 cells, They show deficiencies in expression of the intron-containing mitochondrial genes COX1 and COB, Splicing of COX1 and COB transcripts is impaired in mitochondria lacking m-AAA protease, whilst transcription and translation can proceed in the absence of Yta10p or Yta12p, The function of the m-AAA protease appears to be confined to introns encoding mRNA maturases. Our results reveal an overlapping substrate specificity of the subunits of the m-AAA protease and explain the impaired assembly of respiratory chain complexes by defects in expression of intron-containing genes in mitochondria lacking m-AAA protease.