Control of mitochondrial biogenesis and function by the ubiquitin-proteasome system.
Control of mitochondrial biogenesis and function by the ubiquitin-proteasome system.
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DOI：
10.1098/rsob.170007
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发表时间：
2017-04
期刊：
影响因子：
5.8
通讯作者：
Chacinska A
中科院分区：
文献类型：
--
作者：
Bragoszewski P;Turek M;Chacinska A
线粒体是真核细胞的重要细胞器。线粒体的复杂蛋白质组包括由核和线粒体基因组编码的蛋白质。线粒体蛋白质的生物发生需要它们以具有高错误折叠风险的未折叠状态运输。线粒体蛋白质的错误定位对细胞是有害的。线粒体中的电子传递链是破坏蛋白质的活性氧的来源。线粒体功能障碍与许多病理状况有关，并且与细胞蛋白质稳态（蛋白质稳态）的丧失一起，是衰老和与衰老相关的变性疾病的标志。神经退行性疾病，如阿尔茨海默病和帕金森病的发病机制与线粒体和蛋白质稳态失败有关。因此，线粒体蛋白需要复杂的监视机制。虽然线粒体形成蛋白酶体专属区室，但多条证据表明胞质泛素-蛋白酶体系统（UPS）在线粒体蛋白质的质量控制中起着至关重要的作用。蛋白酶体影响线粒体蛋白质的生物发生和成熟阶段。UPS的作用不仅仅是去除受损的蛋白质，还包括调整线粒体蛋白质组组成、调节细胞器动力学和保护细胞内稳态免受线粒体功能衰竭的影响。反过来，线粒体活性和线粒体功能障碍调节UPS的活性，在细胞水平上具有影响。
Mitochondria are pivotal organelles in eukaryotic cells. The complex proteome of mitochondria comprises proteins that are encoded by nuclear and mitochondrial genomes. The biogenesis of mitochondrial proteins requires their transport in an unfolded state with a high risk of misfolding. The mislocalization of mitochondrial proteins is deleterious to the cell. The electron transport chain in mitochondria is a source of reactive oxygen species that damage proteins. Mitochondrial dysfunction is linked to many pathological conditions and, together with the loss of cellular protein homeostasis (proteostasis), are hallmarks of ageing and ageing-related degeneration diseases. The pathogenesis of neurodegenerative disorders, such as Alzheimer's disease and Parkinson's disease, has been associated with mitochondrial and proteostasis failure. Thus, mitochondrial proteins require sophisticated surveillance mechanisms. Although mitochondria form a proteasome-exclusive compartment, multiple lines of evidence indicate a crucial role for the cytosolic ubiquitin–proteasome system (UPS) in the quality control of mitochondrial proteins. The proteasome affects mitochondrial proteins at stages of their biogenesis and maturity. The effects of the UPS go beyond the removal of damaged proteins and include the adjustment of mitochondrial proteome composition, the regulation of organelle dynamics and the protection of cellular homeostasis against mitochondrial failure. In turn, mitochondrial activity and mitochondrial dysfunction adjust the activity of the UPS, with implications at the cellular level.