Eukaryotic cells have evolved extensive protein quality-control mechanisms to remove faulty translation products. Here, we show that yeast cells continually produce faulty mitochondrial polypeptides that stall on the ribosome during translation but are imported into the mitochondria. The cytosolic protein Vms1, together with the E3 ligase Ltn1, protects against the mitochondrial toxicity of these proteins and maintains cell viability under respiratory conditions. In the absence of these factors, stalled polypeptides aggregate after import and sequester critical mitochondrial chaperone and translation machinery. Aggregation depends on C-terminal alanyl/threonyl sequences (CAT-tails) that are attached to stalled polypeptides on 60S ribosomes by Rqc2. Vms1 binds to 60S ribosomes at the mitochondrial surface and antagonizes Rqc2, thereby facilitating import, impeding aggregation, and directing aberrant polypeptides to intra-mitochondrial quality control. Vms1 is a key component of a rescue pathway for ribosome-stalled mitochondrial polypeptides that are inaccessible to ubiquitylation due to coupling of translation and translocation.

中文翻译：

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胞质蛋白Vms1将核糖体质量控制与线粒体和细胞体内平衡联系起来。

真核细胞已进化出广泛的蛋白质质量控​​制机制，以消除错误的翻译产物。在这里，我们显示酵母细胞不断产生有缺陷的线粒体多肽，这些多肽在翻译过程中停滞在核糖体上，但被导入线粒体中。胞质蛋白Vms1与E3连接酶Ltn1共同保护这些蛋白的线粒体毒性，并在呼吸条件下维持细胞活力。在没有这些因素的情况下，停滞的多肽在导入并隔离关键的线粒体伴侣和翻译机制后聚集。聚集取决于通过Rqc2连接到60S核糖体上失速多肽的C末端丙氨酰/苏氨酰序列（CAT-tails）。Vms1在线粒体表面与60S核糖体结合并拮抗Rqc2，从而促进导入，阻止聚集，并指导异常多肽进行线粒体内质量控制。Vms1是核糖体沉淀的线粒体多肽拯救途径的关键组成部分，由于翻译和易位的耦合，泛素化无法到达。