Cell Biology, University of Kaiserslautern, Kaiserslautern, Germany.
Molecular Genetics, University of Kaiserslautern, Kaiserslautern, Germany.
EMBO Rep. 2024 Apr;25(4):2071-2096. doi: 10.1038/s44319-024-00113-w. Epub 2024 Apr 2.
Most mitochondrial proteins are synthesized on cytosolic ribosomes and imported into mitochondria in a post-translational reaction. Mitochondrial precursor proteins which use the ER-SURF pathway employ the surface of the endoplasmic reticulum (ER) as an important sorting platform. How they reach the mitochondrial import machinery from the ER is not known. Here we show that mitochondrial contact sites play a crucial role in the ER-to-mitochondria transfer of precursor proteins. The ER mitochondria encounter structure (ERMES) and Tom70, together with Djp1 and Lam6, are part of two parallel and partially redundant ER-to-mitochondria delivery routes. When ER-to-mitochondria transfer is prevented by loss of these two contact sites, many precursors of mitochondrial inner membrane proteins are left stranded on the ER membrane, resulting in mitochondrial dysfunction. Our observations support an active role of the ER in mitochondrial protein biogenesis.
大多数线粒体蛋白是在细胞质核糖体上合成的，并在翻译后反应中被导入线粒体。使用内质网-表面反应（ER-SURF）途径的线粒体前体蛋白利用内质网（ER）的表面作为一个重要的分拣平台。它们如何从 ER 到达线粒体导入机制尚不清楚。在这里，我们表明线粒体接触点在 ER 到线粒体前体蛋白的转移中起着至关重要的作用。内质网-线粒体接触结构（ERMES）和 Tom70 ，以及 Djp1 和 Lam6 ，是两条平行且部分冗余的 ER 到线粒体递呈途径的一部分。当这两个接触点的缺失阻止 ER 到线粒体的转移时，许多线粒体内膜蛋白的前体滞留在 ER 膜上，导致线粒体功能障碍。我们的观察结果支持 ER 在线粒体蛋白生物发生中的积极作用。
