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肾脏自噬调节中的mTOR信号传导

mTOR signaling in autophagy regulation in the kidney.

作者信息

Inoki Ken

机构信息

Life Sciences Institute, Department of Molecular and Integrative Physiology, Division of Nephrology, Department of Internal Medicine, University of Michigan, Ann Arbor, MI.

出版信息

Semin Nephrol. 2014 Jan;34(1):2-8. doi: 10.1016/j.semnephrol.2013.11.002. Epub 2013 Nov 21.

Abstract

Cells possess adaptive biosynthetic systems to maintain cellular energy levels for survival under adverse environmental conditions. Autophagy is an evolutionarily conserved cellular catabolic process that breaks down and recycles cytosolic material including macromolecules and organelles through lysosomal degradation. This catabolic process, represented by macroautophagy, is induced by a variety of cellular stresses such as nutrient starvation, which causes a shortage of cellular energy for cells to maintain cellular homeostasis and essential biological activities. In contrast, upon nutrient availability, cells stimulate anabolic processes. The mechanistic/mammalian target of rapamycin, a serine/threonine protein kinase, is a key player in stimulating cellular anabolism in response to nutrients and growth factors, and plays a crucial role in suppressing autophagy activity. Growing evidence has suggested that autophagy activity is required for the maintenance and physiological functions of renal cells including proximal tubular cells and podocytes. In this article, we discuss recent progress in the regulation of autophagy by mechanistic/mammalian target of rapamycin signaling.

摘要

细胞拥有适应性生物合成系统,以在不利环境条件下维持细胞能量水平以确保生存。自噬是一种进化上保守的细胞分解代谢过程,它通过溶酶体降解来分解和回收包括大分子和细胞器在内的胞质物质。这种以巨自噬为代表的分解代谢过程,由多种细胞应激诱导,如营养饥饿,这会导致细胞能量短缺,使细胞难以维持细胞内稳态和基本生物学活性。相反,在营养充足时,细胞会刺激合成代谢过程。雷帕霉素作用机制/哺乳动物靶点,一种丝氨酸/苏氨酸蛋白激酶,是响应营养物质和生长因子刺激细胞合成代谢的关键参与者,并在抑制自噬活性中起关键作用。越来越多的证据表明,自噬活性对于包括近端肾小管细胞和足细胞在内的肾细胞的维持和生理功能是必需的。在本文中,我们讨论了雷帕霉素作用机制/哺乳动物靶点信号通路对自噬调节的最新进展。

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