Bragoszewski Piotr, Turek Michal, Chacinska Agnieszka
Laboratory of Mitochondrial Biogenesis, International Institute of Molecular and Cell Biology, Ks. Trojdena 4, 02-109 Warsaw, Poland
Laboratory of Mitochondrial Biogenesis, International Institute of Molecular and Cell Biology, Ks. Trojdena 4, 02-109 Warsaw, Poland.
Open Biol. 2017 Apr;7(4). doi: 10.1098/rsob.170007.
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.
线粒体是真核细胞中的关键细胞器。线粒体复杂的蛋白质组由核基因组和线粒体基因组编码的蛋白质组成。线粒体蛋白质的生物合成需要它们以未折叠状态运输，这存在很高的错误折叠风险。线粒体蛋白质的错误定位对细胞有害。线粒体中的电子传递链是产生会损伤蛋白质的活性氧的来源。线粒体功能障碍与许多病理状况相关，并且与细胞蛋白质稳态（蛋白质平衡）的丧失一起，是衰老和衰老相关退行性疾病的标志。神经退行性疾病，如阿尔茨海默病和帕金森病的发病机制，与线粒体和蛋白质平衡功能障碍有关。因此，线粒体蛋白质需要复杂的监测机制。尽管线粒体形成了一个仅含蛋白酶体的区室，但多条证据表明胞质泛素 - 蛋白酶体系统（UPS）在线粒体蛋白质质量控制中起关键作用。蛋白酶体在其生物合成和成熟阶段影响线粒体蛋白质。UPS的作用不仅限于去除受损蛋白质，还包括调整线粒体蛋白质组组成、调节细胞器动态以及保护细胞稳态免受线粒体功能障碍的影响。反过来，线粒体活性和线粒体功能障碍会调整UPS的活性，这在细胞水平上具有重要意义。
