Insertion Defects of Mitochondrially Encoded Proteins Burden the Mitochondrial Quality Control System.
Insertion Defects of Mitochondrially Encoded Proteins Burden the Mitochondrial Quality Control System.
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作者：
Vargas Möller-Hergt B;Carlström A;Suhm T;Ott M
线粒体蛋白质组包含来自两个不同遗传系统的蛋白质。蛋白质要么在细胞质中合成并输入细胞器的不同区室，要么直接在线粒体基质中产生。为了确保蛋白质稳态，蛋白质由线粒体质量控制系统监控，这将降解非天然多肽。有缺陷的线粒体膜蛋白会被膜结合的 AAA 蛋白酶降解。这些蛋白酶受到促进蛋白质周转或防止其降解的因素的调节。在这里，我们通过质量控制系统确定了线粒体核糖体受体 Mrx15 和 Mba1 之间的遗传相互作用。我们发现，Mrx15 和 i-AAA 蛋白酶 Mgr1 和 Mgr3 调节因子同时缺失会引起呼吸缺陷。令人惊讶的是，缺乏 Mrx15 的突变体对蛋白毒性胁迫具有更强的耐受性。此外，缺失 MBA1 后，酵母细胞对蛋白毒性应激变得高度敏感。与 Mrx15 相反，Mba1 与 m-AAA 和 i-AAA 蛋白酶的调节者合作。综上所述，这些结果表明膜蛋白插入和线粒体 AAA 蛋白酶在功能上耦合，可能反映了线粒体蛋白合成过程中的早期质量控制步骤。
The mitochondrial proteome contains proteins from two different genetic systems. Proteins are either synthesized in the cytosol and imported into the different compartments of the organelle or directly produced in the mitochondrial matrix. To ensure proteostasis, proteins are monitored by the mitochondrial quality control system, which will degrade non-native polypeptides. Defective mitochondrial membrane proteins are degraded by membrane-bound AAA-proteases. These proteases are regulated by factors promoting protein turnover or preventing their degradation. Here we determined genetic interactions between the mitoribosome receptors Mrx15 and Mba1 with the quality control system. We show that simultaneous absence of Mrx15 and the regulators of the i-AAA protease Mgr1 and Mgr3 provokes respiratory deficiency. Surprisingly, mutants lacking Mrx15 were more tolerant against proteotoxic stress. Furthermore, yeast cells became hypersensitive against proteotoxic stress upon deletion of MBA1. Contrary to Mrx15, Mba1 cooperates with the regulators of the m-AAA and i-AAA proteases. Taken together, these results suggest that membrane protein insertion and mitochondrial AAA-proteases are functionally coupled, possibly reflecting an early quality control step during mitochondrial protein synthesis.
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影响因子：
4.8
作者：
Hallstrom, TC;Moye-Rowley, WS
通讯作者：
Moye-Rowley, WS
影响因子：
3.3
作者：
Moller-Hergt, Braulio Vargas;Carlstrom, Andreas;Ott, Martin
通讯作者：
Ott, Martin
影响因子：
64.5
作者：
Arlt, H;Tauer, R;Langer, T
通讯作者：
Langer, T
影响因子：
3.3
作者：
Dunn, CD;Lee, MS;Jensen, RE
通讯作者：
Jensen, RE
DOI：
10.1126/science.aao0464
发表时间：
2017-11-03
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Puchades C;Rampello AJ;Shin M;Giuliano CJ;Wiseman RL;Glynn SE;Lander GC
通讯作者：
Lander GC