The ER-SURF pathway uses ER-mitochondria contact sites for protein targeting to mitochondria

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 encounter structure (ERMES) and Tom70 are part of two cooperative and partially redundant ER-to-mitochondria transfer routes. If the ER-to-mitochondria transfer is prevented, many mitochondrial precursor proteins accumulate non-productively on the ER surface, resulting in mitochondrial dysfunction. Our observations support an active role of the ER in mitochondrial protein biogenesis.

绝大多数线粒体蛋白均在胞质核糖体上合成，并通过翻译后转运过程导入线粒体。采用ER-SURF通路（ER-SURF pathway）的线粒体前体蛋白，以内质网（endoplasmic reticulum, ER）膜表面作为关键分选平台。目前学界尚未明确这类前体蛋白如何从内质网转运至线粒体蛋白导入复合体。本研究发现，线粒体接触位点在前体蛋白从内质网到线粒体的转运过程中发挥关键作用。ER接触结构（ER encounter structure, ERMES）与Tom70是两条协同且存在部分功能冗余的内质网-线粒体转运通路的组成部分。若阻断内质网-线粒体的转运过程，大量线粒体前体蛋白会在内质网膜表面非功能性积累，进而引发线粒体功能障碍。本研究结果证实，内质网在线粒体蛋白质生物发生过程中具有主动调控的重要作用。