Mitochondrial protein import: Mia40 facilitates Tim22 translocation into the inner membrane of mitochondria.
Mitochondrial protein import: Mia40 facilitates Tim22 translocation into the inner membrane of mitochondria.
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DOI：
10.1091/mbc.e12-09-0649
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发表时间：
2013-03
影响因子：
3.3
通讯作者：
Chacinska A
中科院分区：
文献类型：
--
作者：
Wrobel L;Trojanowska A;Sztolsztener ME;Chacinska A
MIA途径控制膜间隙蛋白的定位和氧化折叠。这项研究报告，MIA途径参与线粒体内膜蛋白Tim22的运输，从而扩大了已知的功能MIA的内膜蛋白的生物合成。线粒体膜间空间组装（MIA）途径通常被认为致力于定位于线粒体膜间空间的蛋白质的氧化还原依赖性输入和生物合成。氧化还原酶Mia40是负责将二硫键转移到膜间空间前体蛋白的途径的中心组分，导致其氧化折叠。在这里，我们提出的第一个证据表明，Mia40的功能不限于运输和氧化折叠的膜间空间蛋白。我们确定Tim22，一个多跨膜蛋白和内膜的TIM22转位酶的核心组成部分，作为一个蛋白质与半胱氨酸残基进行氧化过程中Tim22的生物发生。我们发现，Mia40参与了Tim22的生物起源和复杂组装。Tim22在输入线粒体后与Mia40形成二硫键结合的中间体。令人感兴趣的是，Mia40也通过非共价相互作用结合Tim22前体。我们认为Mia40不仅负责二硫键的形成，而且还协助Tim22蛋白整合到线粒体内膜中。
The MIA pathway governs the localization and oxidative folding of intermembrane space proteins. This study reports that the MIA pathway is involved in the transport of mitochondrial inner membrane protein Tim22, thereby broadening the known functions of MIA to the biogenesis of inner membrane proteins. The mitochondrial intermembrane space assembly (MIA) pathway is generally considered to be dedicated to the redox-dependent import and biogenesis of proteins localized to the intermembrane space of mitochondria. The oxidoreductase Mia40 is a central component of the pathway responsible for the transfer of disulfide bonds to intermembrane space precursor proteins, causing their oxidative folding. Here we present the first evidence that the function of Mia40 is not restricted to the transport and oxidative folding of intermembrane space proteins. We identify Tim22, a multispanning membrane protein and core component of the TIM22 translocase of inner membrane, as a protein with cysteine residues undergoing oxidation during Tim22 biogenesis. We show that Mia40 is involved in the biogenesis and complex assembly of Tim22. Tim22 forms a disulfide-bonded intermediate with Mia40 upon import into mitochondria. Of interest, Mia40 binds the Tim22 precursor also via noncovalent interactions. We propose that Mia40 not only is responsible for disulfide bond formation, but also assists the Tim22 protein in its integration into the inner membrane of mitochondria.