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线粒体复合物揭示蛋白质输入的质量控制途径
2023-01-31 13:53

德国弗莱堡大学Bernd Fakler等研究人员合作发现,线粒体复合物揭示蛋白质输入的质量控制途径。这一研究成果于2023年1月25日在线发表在国际学术期刊《自然》上。

通过超过90%的酵母线粒体蛋白质组的高分辨率复杂组分析,研究人员报告了线粒体蛋白质组合的定量图谱,称为MitCOM。对MitCOM数据集的分析解决了5200个蛋白质峰值,平均每个蛋白质有6个峰值,并证明了线粒体蛋白质组合的显著复杂性,具有呼吸、代谢、生物发生、动力学、调节和氧化还原过程的不同外观。研究人员检测到多个互作蛋白,包括细胞质核糖体与线粒体受体、抗增殖蛋白支架和呼吸链复合物。在线粒体蛋白质进入通道工作的质量控制因子的鉴定揭示了蛋白质前泛素化,去泛素化和降解的途径。肽基-tRNA水解酶Pth2与进入通道之间的相互作用导致了去除前蛋白的组成型途径的阐明。MitCOM数据集可通过交互式档案查看器访问,并且是线粒体机器和途径的识别、组织和交互的综合资源。

据介绍,线粒体在细胞能量学、代谢、信号传递和质量控制中起着至关重要的作用。它们包含大约1000种不同的蛋白质,通常组装成复合物和超复合物,如呼吸复合物和前蛋白易位酶。线粒体蛋白质组的组成已被鉴定;然而,对于蛋白质组的主要部分,线粒体蛋白的稳定和动态组合的组织尚不清楚。

附:英文原文

Title: Mitochondrial complexome reveals quality-control pathways of protein import

Author: Schulte, Uwe, den Brave, Fabian, Haupt, Alexander, Gupta, Arushi, Song, Jiyao, Mller, Catrin S., Engelke, Jeannine, Mishra, Swadha, Mrtensson, Christoph, Ellenrieder, Lars, Priesnitz, Chantal, Straub, Sebastian P., Doan, Kim Nguyen, Kulawiak, Bogusz, Bildl, Wolfgang, Rampelt, Heike, Wiedemann, Nils, Pfanner, Nikolaus, Fakler, Bernd, Becker, Thomas

Issue&Volume: 2023-01-25

Abstract: Mitochondria have crucial roles in cellular energetics, metabolism, signalling and quality control1,2,3,4. They contain around 1,000 different proteins that often assemble into complexes and supercomplexes such as respiratory complexes and preprotein translocases1,3,4,5,6,7. The composition of the mitochondrial proteome has been characterized1,3,5,6; however, the organization of mitochondrial proteins into stable and dynamic assemblies is poorly understood for major parts of the proteome1,4,7. Here we report quantitative mapping of mitochondrial protein assemblies using high-resolution complexome profiling of more than 90% of the yeast mitochondrial proteome, termed MitCOM. An analysis of the MitCOM dataset resolves >5,200 protein peaks with an average of six peaks per protein and demonstrates a notable complexity of mitochondrial protein assemblies with distinct appearance for respiration, metabolism, biogenesis, dynamics, regulation and redox processes. We detect interactors of the mitochondrial receptor for cytosolic ribosomes, of prohibitin scaffolds and of respiratory complexes. The identification of quality-control factors operating at the mitochondrial protein entry gate reveals pathways for preprotein ubiquitylation, deubiquitylation and degradation. Interactions between the peptidyl-tRNA hydrolase Pth2 and the entry gate led to the elucidation of a constitutive pathway for the removal of preproteins. The MitCOM dataset—which is accessible through an interactive profile viewer—is a comprehensive resource for the identification, organization and interaction of mitochondrial machineries and pathways.

DOI: 10.1038/s41586-022-05641-w

Source: https://www.nature.com/articles/s41586-022-05641-w

Nature:《自然》,创刊于1869年。隶属于施普林格·自然出版集团,最新IF:69.504
官方网址:http://www.nature.com/
投稿链接:http://www.nature.com/authors/submit_manuscript.html


本期文章:《自然》:Online/在线发表

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