Department of Chemistry, Biochemistry and Pharmaceutical Sciences, University of Bern, Freiestrasse 3, Bern, CH-3012, Switzerland.
Faculty of Chemistry and Pharmacy, Department of Biochemistry, Theodor Boveri-Institute, University of Würzburg, 97074, Würzburg, Germany.
Nat Commun. 2022 Jun 2;13(1):3084. doi: 10.1038/s41467-022-30748-z.
Mitochondrial protein import in the parasitic protozoan Trypanosoma brucei is mediated by the atypical outer membrane translocase, ATOM. It consists of seven subunits including ATOM69, the import receptor for hydrophobic proteins. Ablation of ATOM69, but not of any other subunit, triggers a unique quality control pathway resulting in the proteasomal degradation of non-imported mitochondrial proteins. The process requires a protein of unknown function, an E3 ubiquitin ligase and the ubiquitin-like protein (TbUbL1), which all are recruited to the mitochondrion upon ATOM69 depletion. TbUbL1 is a nuclear protein, a fraction of which is released to the cytosol upon triggering of the pathway. Nuclear release is essential as cytosolic TbUbL1 can bind mislocalised mitochondrial proteins and likely transfers them to the proteasome. Mitochondrial quality control has previously been studied in yeast and metazoans. Finding such a pathway in the highly diverged trypanosomes suggests such pathways are an obligate feature of all eukaryotes.
线粒体蛋白在寄生原生动物布氏锥虫中的输入是由非典型的外膜转运蛋白 ATOM 介导的。它由七个亚基组成，包括 ATOM69，它是疏水性蛋白的输入受体。ATOM69 的缺失，但不是任何其他亚基的缺失，会触发一种独特的质量控制途径，导致未输入的线粒体蛋白的蛋白酶体降解。该过程需要一种未知功能的蛋白质、一种 E3 泛素连接酶和泛素样蛋白（TbUbL1），这些蛋白在 ATOM69 耗尽时都被招募到线粒体。TbUbL1 是一种核蛋白，其中一部分在该途径被触发时被释放到细胞质中。核释放是必需的，因为细胞质 TbUbL1 可以结合定位错误的线粒体蛋白，并可能将它们转移到蛋白酶体。线粒体质量控制以前在酵母和后生动物中进行了研究。在高度分化的锥虫中发现这样的途径表明，这样的途径是所有真核生物的强制性特征。
