Mesh : Mitochondrial Membranes / metabolism Saccharomyces cerevisiae Proteins / metabolism genetics Mitochondria / metabolism Saccharomyces cerevisiae / metabolism Mitochondrial Proteins / metabolism genetics Protein Transport Mitochondrial Precursor Protein Import Complex Proteins Mitochondrial Membrane Transport Proteins / metabolism genetics Proteome / metabolism

来  源:   DOI:10.1083/jcb.202307036

Abstract:
The outer mitochondrial membrane (OMM) creates a boundary that imports most of the mitochondrial proteome while removing extraneous or damaged proteins. How the OMM senses aberrant proteins and remodels to maintain OMM integrity remains unresolved. Previously, we identified a mitochondrial remodeling mechanism called the mitochondrial-derived compartment (MDC) that removes a subset of the mitochondrial proteome. Here, we show that MDCs specifically sequester proteins localized only at the OMM, providing an explanation for how select mitochondrial proteins are incorporated into MDCs. Remarkably, selective sorting into MDCs also occurs within the OMM, as subunits of the translocase of the outer membrane (TOM) complex are excluded from MDCs unless assembly of the TOM complex is impaired. Considering that overloading the OMM with mitochondrial membrane proteins or mistargeted tail-anchored membrane proteins induces MDCs to form and sequester these proteins, we propose that one functional role of MDCs is to create an OMM-enriched trap that segregates and sequesters excess proteins from the mitochondrial surface.
摘要:
线粒体外膜(OMM)创建了一个边界,该边界导入大多数线粒体蛋白质组,同时去除外来或受损的蛋白质。OMM如何感知异常蛋白质和重塑以维持OMM完整性仍未解决。以前,我们确定了一种线粒体重塑机制,称为线粒体衍生区室(MDC),该机制可去除线粒体蛋白质组的一部分。这里,我们显示MDC特异性地隔离仅位于OMM的蛋白质,为选择线粒体蛋白如何掺入MDC提供解释。值得注意的是,选择性分选到MDC中也发生在OMM中,除非TOM复合物的组装受损,否则将外膜(TOM)复合物的转位酶亚基从MDC中排除。考虑到用线粒体膜蛋白或错误定位的尾部锚定膜蛋白使OMM过载会诱导MDC形成和隔离这些蛋白,我们认为MDCs的一个功能作用是创建一个OMM富集的陷阱,该陷阱从线粒体表面分离和隔离过量的蛋白质。
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