Interrelation between protein synthesis, proteostasis and life span.
Interrelation between protein synthesis, proteostasis and life span.
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DOI：
10.2174/1389202915666140210210542
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发表时间：
2014-02
期刊：
影响因子：
2.6
通讯作者：
Kirstein-Miles J
中科院分区：
文献类型：
--
作者：
Arnsburg K;Kirstein-Miles J
新合成蛋白质的产生是蛋白质稳态的关键过程，它启动了蛋白质的生物合成通量，从而决定了蛋白质组的组成、稳定性和功能。蛋白质合成在多个水平上受到高度调节，以使蛋白质组适应环境和生理挑战，如衰老和蛋白质毒性条件。蛋白质折叠条件的不平衡被细胞感知，然后触发一系列旨在恢复蛋白质折叠平衡的信号通路。在压力下重新平衡蛋白质平衡的一个调节节点是蛋白质合成本身的控制。翻译作为对蛋白质折叠平衡的扰动的直接反应而减少，这种扰动可以在细胞器（如内质网和线粒体）以及细胞器中观察到。由于蛋白质合成的减少与寿命的增加有关，调节蛋白质合成的信号通路可能是治疗年龄相关疾病的假定靶点。真核细胞已经进化出一个复杂的蛋白质合成调节系统，本文将总结细胞在应激下调节mRNA翻译的策略及其对寿命的影响。
The production of newly synthesized proteins is a key process of protein homeostasis that initiates the biosynthetic flux of proteins and thereby determines the composition, stability and functionality of the proteome. Protein synthesis is highly regulated on multiple levels to adapt the proteome to environmental and physiological challenges such as aging and proteotoxic conditions. Imbalances of protein folding conditions are sensed by the cell that then trigger a cascade of signaling pathways aiming to restore the protein folding equilibrium. One regulatory node to rebalance proteostasis upon stress is the control of protein synthesis itself. Translation is reduced as an immediate response to perturbations of the protein folding equilibrium that can be observed in the cytosol as well as in the organelles such as the endoplasmatic reticulum and mitochondria. As reduction of protein synthesis is linked to life span increase, the signaling pathways regu-lating protein synthesis might be putative targets for treatments of age-related diseases. Eukaryotic cells have evolved a complex system for protein synthesis regulation and this review will summarize cellular strategies to regulate mRNA translation upon stress and its impact on longevity.