Buneeva O A, Kopylov A T, Medvedev A E
Institute of Biomedical Chemistry, Moscow, Russia.
Biomed Khim. 2020 Feb;66(2):138-144. doi: 10.18097/PBMC20206602138.
Good evidence exists that the ubiquitin-proteasome system (UPS) plays an important role in degradation of mitochondrial proteins and membrane proteins associated with mitochondria (MAM proteins). Mitochondria contain all components of the ubiquitin-conjugating system, which are necessary for the attachment of ubiquitin molecules to target proteins, subjected to subsequent degradation in proteasomes. An important stage in the delivery of proteins for proteolytic degradation in proteasomes is their interaction with ubiquitin receptors located on the regulatory subunit (19S) of the proteasome: the Rpn10 or Rpn13 subunit. These subunits make basically the same contribution to the subsequent translocation of target proteins to the core part of the proteasome. A comparative study of mouse brain mitochondrial subproteomes bound to Rpn10 and Rpn13 subunits revealed a high specificity of the repertoire of Rpn10 and Rpn13-binding proteins. Moreover, proteins, for which mitochondrial localization or association with mitochondrial membranes was previously shown, prevailed in the case of using the Rpn13 subunit as an affinity ligand (Rpn13-binding proteins). This suggests that Rpn10 and Rpn13 play different roles in the degradation of mitochondrial proteins and MAM.
有充分证据表明，泛素 - 蛋白酶体系统（UPS）在降解线粒体蛋白和与线粒体相关的膜蛋白（线粒体相关膜蛋白，MAM蛋白）中发挥着重要作用。线粒体包含泛素缀合系统的所有组分，这些组分对于将泛素分子附着到靶蛋白上是必需的，随后靶蛋白会在蛋白酶体中被降解。在蛋白酶体中进行蛋白水解降解的一个重要阶段是它们与位于蛋白酶体调节亚基（19S）上的泛素受体相互作用：Rpn10或Rpn13亚基。这些亚基对随后将靶蛋白转运到蛋白酶体核心部分的作用基本相同。一项对与Rpn10和Rpn13亚基结合的小鼠脑线粒体亚蛋白质组的比较研究揭示了Rpn10和Rpn13结合蛋白库的高度特异性。此外，在使用Rpn13亚基作为亲和配体（Rpn13结合蛋白）的情况下，先前已显示出线粒体定位或与线粒体膜相关的蛋白质占主导。这表明Rpn10和Rpn13在降解线粒体蛋白和MAM中发挥不同作用。
