PDF(Pubmed)
Abstract：
Cellular proteostasis requires transport of polypeptides across membranes. Although defective transport processes trigger cytosolic rescue and quality control mechanisms that clear translocases and membranes from unproductive cargo, proteins that are synthesized within mitochondria are not accessible to these mechanisms. Mitochondrial-encoded proteins are inserted cotranslationally into the inner membrane by the conserved insertase OXA1L. Here, we identify TMEM126A as a OXA1L-interacting protein. TMEM126A associates with mitochondrial ribosomes and translation products. Loss of TMEM126A leads to the destabilization of mitochondrial translation products, triggering an inner membrane quality control process, in which newly synthesized proteins are degraded by the mitochondrial iAAA protease. Our data reveal that TMEM126A cooperates with OXA1L in protein insertion into the membrane. Upon loss of TMEM126A, the cargo-blocked OXA1L insertase complexes undergo proteolytic clearance by the iAAA protease machinery together with its cargo.
摘要：
细胞蛋白质停滞需要多肽跨膜转运。尽管有缺陷的运输过程会触发胞质救援和质量控制机制，从而清除非生产性货物中的易位酶和膜，在线粒体内合成的蛋白质无法通过这些机制获得。线粒体编码的蛋白质通过保守的插入酶OXA1L共翻译插入内膜。这里,我们将TMEM126A鉴定为OXA1L相互作用蛋白。TMEM126A与线粒体核糖体和翻译产物结合。TMEM126A的丢失导致线粒体翻译产物的不稳定,触发内膜质量控制过程，其中新合成的蛋白质被线粒体iAAA蛋白酶降解。我们的数据揭示了TMEM126A与OXA1L在蛋白质插入膜中的合作。TMEM126A丢失后，货物阻断的OXA1L插入酶复合物与其货物一起通过iAAA蛋白酶机械进行蛋白水解清除。
