Ellenrieder Lars, Mårtensson Christoph U, Becker Thomas
Biol Chem. 2015 Nov;396(11):1199-213. doi: 10.1515/hsz-2015-0170.
Proteins of the mitochondrial outer membrane are synthesized as precursors on cytosolic ribosomes and sorted via internal targeting sequences to mitochondria. Two different types of integral outer membrane proteins exist: proteins with a transmembrane β-barrel and proteins embedded by a single or multiple α-helices. The import pathways of these two types of membrane proteins differ fundamentally. Precursors of β-barrel proteins are first imported across the outer membrane via the translocase of the outer membrane (TOM complex). The TOM complex is coupled to the sorting and assembly machinery (SAM complex), which catalyzes folding and membrane insertion of these precursors. The mitochondrial import machinery (MIM complex) promotes import of proteins with multiple α-helical membrane spans. Depending on the topology precursors of proteins with a single α-helical membrane anchor are imported via several distinct routes. We summarize current models and open questions of biogenesis of mitochondrial outer membrane proteins and discuss the impact of malfunctions of protein sorting on the development of diseases.
线粒体外膜蛋白最初在胞质核糖体上以前体形式合成，并通过内部靶向序列分选至线粒体。线粒体外膜存在两种不同类型的整合蛋白：具有跨膜β-桶状结构的蛋白和由单个或多个α-螺旋嵌入的蛋白。这两种膜蛋白的导入途径存在根本差异。β-桶状蛋白前体首先通过外膜转位酶（TOM复合体）穿过外膜。TOM复合体与分选和组装机制（SAM复合体）相连，后者催化这些前体的折叠和膜插入。线粒体导入机制（MIM复合体）促进具有多个α-螺旋跨膜结构的蛋白的导入。根据拓扑结构，具有单个α-螺旋膜锚定的蛋白前体通过几种不同途径导入。我们总结了线粒体外膜蛋白生物发生的当前模型和未解决的问题，并讨论了蛋白质分选功能异常对疾病发展的影响。
