Korovila Ioanna, Hugo Martín, Castro José Pedro, Weber Daniela, Höhn Annika, Grune Tilman, Jung Tobias
Department of Molecular Toxicology, German Institute of Human Nutrition Potsdam-Rehbruecke (DIfE), 14558 Nuthetal, Germany.
Department of Molecular Toxicology, German Institute of Human Nutrition Potsdam-Rehbruecke (DIfE), 14558 Nuthetal, Germany; German Center for Diabetes Research (DZD), 85764 Muenchen-Neuherberg, Germany; Faculty of Medicine, Department of Biomedicine, University of Porto, 4200-319, Portugal; Institute for Innovation and Health Research (I3S), Aging and Stress Group, R. Alfredo Allen, 4200-135 Porto, Portugal.
Redox Biol. 2017 Oct;13:550-567. doi: 10.1016/j.redox.2017.07.008. Epub 2017 Jul 12.
The production of reactive species is an inevitable by-product of metabolism and thus, life itself. Since reactive species are able to damage cellular structures, especially proteins, as the most abundant macromolecule of mammalian cells, systems are necessary which regulate and preserve a functional cellular protein pool, in a process termed "proteostasis". Not only the mammalian protein pool is subject of a constant turnover, organelles are also degraded and rebuild. The most important systems for these removal processes are the "ubiquitin-proteasomal system" (UPS), the central proteolytic machinery of mammalian cells, mainly responsible for proteostasis, as well as the "autophagy-lysosomal system", which mediates the turnover of organelles and large aggregates. Many age-related pathologies and the aging process itself are accompanied by a dysregulation of UPS, autophagy and the cross-talk between both systems. This review will describe the sources and effects of oxidative stress, preservation of cellular protein- and organelle-homeostasis and the effects of aging on proteostasis in mammalian cells.
活性物质的产生是新陈代谢乃至生命本身不可避免的副产物。由于活性物质能够破坏细胞结构，尤其是蛋白质（作为哺乳动物细胞中最丰富的大分子），因此需要一些系统来调节并维持一个功能性的细胞蛋白质库，这一过程称为“蛋白质稳态”。不仅哺乳动物的蛋白质库处于持续更新之中，细胞器也会被降解并重新构建。这些清除过程最重要的系统是“泛素-蛋白酶体系统”（UPS），它是哺乳动物细胞的核心蛋白水解机制，主要负责蛋白质稳态，还有“自噬-溶酶体系统”，它介导细胞器和大聚集体的更新。许多与年龄相关的病症以及衰老过程本身都伴随着UPS、自噬以及这两个系统之间相互作用的失调。本综述将描述氧化应激的来源和影响、细胞蛋白质和细胞器稳态的维持，以及衰老对哺乳动物细胞蛋白质稳态的影响。
