Ubiquitin-Dependent Degradation of Mitochondrial Proteins Regulates Energy Metabolism
Ubiquitin-Dependent Degradation of Mitochondrial Proteins Regulates Energy Metabolism
复制标题
DOI：
10.1016/j.celrep.2018.05.013
复制
发表时间：
2018-06-05
期刊：
影响因子：
8.8
通讯作者：
Benard, Giovanni
中科院分区：
文献类型：
--
作者：
Lavie, Julie;De Belvalet, Harmony;Benard, Giovanni
泛素蛋白酶体系统（UPS）通过降解关键蛋白质来调节许多细胞功能。值得注意的是，UPS在调节线粒体代谢功能中的作用尚不清楚。在这里，我们表明，泛素化发生在不同的线粒体隔间，包括线粒体内膜，和营业额的几种代谢蛋白是UPS依赖。我们特别详细的线粒体泛素化和随后的UPS依赖性降解琥珀酸脱氢酶亚基A（SDHA），发生时SDHA参与线粒体能量代谢最低。我们证明SDHA泛素化发生在细胞器内。此外，我们表明，特异性抑制SDHA降解UPS促进SDHA依赖的耗氧量，并增加ATP，苹果酸和柠檬酸水平。这些发现表明，线粒体代谢机制也受到UPS的调节。
The ubiquitin proteasome system (UPS) regulates many cellular functions by degrading key proteins. Notably, the role of UPS in regulating mitochondrial metabolic functions is unclear. Here, we show that ubiquitination occurs in different mitochondrial compartments, including the inner mitochondrial membrane, and that turnover of several metabolic proteins is UPS dependent. We specifically detailed mitochondrial ubiquitination and subsequent UPS-dependent degradation of succinate dehydrogenase subunit A (SDHA), which occurred when SDHA was minimally involved in mitochondrial energy metabolism. We demonstrate that SDHA ubiquitination occurs inside the organelle. In addition, we show that the specific inhibition of SDHA degradation by UPS promotes SDHA-dependent oxygen consumption and increases ATP, malate, and citrate levels. These findings suggest that the mitochondrial metabolic machinery is also regulated by the UPS.