For the biogenesis of mitochondria, hundreds of proteins need to be targeted from the cytosol into the various compartments of this organelle. The intramitochondrial targeting routes these proteins take to reach their respective location in the organelle are well understood. However, the early targeting processes, from cytosolic ribosomes to the membrane of the organelle, are still largely unknown. In this study, we present evidence that an integral membrane protein of the endoplasmic reticulum (ER), Ema19, plays a role in this process. Mutants lacking Ema19 show an increased stability of mitochondrial precursor proteins, indicating that Ema19 promotes the proteolytic degradation of non-productive precursors. The deletion of Ema19 improves the growth of respiration-deficient cells, suggesting that Ema19-mediated degradation can compete with productive protein import into mitochondria. Ema19 is the yeast representative of a conserved protein family. The human Ema19 homolog is known as sigma 2 receptor or TMEM97. Though its molecular function is not known, previous studies suggested a role of the sigma 2 receptor as a quality control factor in the ER, compatible with our observations about Ema19. More globally, our data provide an additional demonstration of the important role of the ER in mitochondrial protein targeting.

对于线粒体的生物发生，需要将数百种蛋白质从细胞质中靶向到该细胞器的各个隔室中。这些蛋白质到达它们在细胞器中的各自位置所采用的线粒体内靶向路径是众所周知的。然而，从细胞质核糖体到细胞器膜的早期靶向过程仍然很大程度上未知。在这项研究中，我们提供的证据表明内质网 (ER) 的完整膜蛋白 Ema19 在此过程中发挥作用。缺乏 Ema19 的突变体显示线粒体前体蛋白的稳定性增加，表明 Ema19 促进非生产性前体的蛋白水解降解。Ema19 的缺失改善了呼吸缺陷细胞的生长，表明 Ema19 介导的降解可以与进入线粒体的生产性蛋白质竞争。Ema19 是保守蛋白家族的酵母代表。人类 Ema19 同系物被称为 sigma 2 受体或 TMEM97。尽管其分子功能尚不清楚，但先前的研究表明 sigma 2 受体作为 ER 中的质量控制因子的作用，与我们对 Ema19 的观察一致。在全球范围内，我们的数据进一步证明了 ER 在线粒体蛋白质靶向中的重要作用。与我们对 Ema19 的观察一致。在全球范围内，我们的数据进一步证明了 ER 在线粒体蛋白质靶向中的重要作用。与我们对 Ema19 的观察一致。在全球范围内，我们的数据进一步证明了 ER 在线粒体蛋白质靶向中的重要作用。