Autophagy: An Integral Component of the Mammalian Stress Response.
Autophagy: An Integral Component of the Mammalian Stress Response.
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发表时间：
2013-09
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通讯作者：
S. Ryter;A. Choi
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作者：
S. Ryter;A. Choi
哺乳动物细胞和组织通过诱导延长生存的适应性或保护机制来应对化学和物理压力。其中，主要的应激诱导蛋白（热休克蛋白、葡萄糖调节蛋白、血红素加氧酶-1）通过蛋白伴侣和/或抗氧化和抗炎功能提供细胞保护。近年来，人们越来越清楚，自噬是一种基因编程且进化保守的细胞过程，代表着另一种对细胞应激的适应性反应。在自噬过程中，细胞溶质物质，包括细胞器、蛋白质和外来病原体，被隔离在称为自噬体的膜结合囊泡中，然后输送到溶酶体进行降解。通过细胞生化物质的回收，自噬提供了一种适应饥饿的机制。最近的研究发现了选择性自噬途径，将不同的货物靶向自噬体，包括清除聚集蛋白和去除功能失调的线粒体（线粒体自噬）的机制。自噬可由多种形式的化学和物理应激诱导，包括内质网应激和氧化应激，并在哺乳动物应激反应中发挥着不可或缺的作用。了解自噬与其他应激诱导系统的相互作用和共同调节将有助于设计和实施针对该途径的治疗方法。
Mammalian cells and tissues respond to chemical and physical stress by inducing adaptive or protective mechanisms that prolong survival. Among these, the major stress inducible proteins (heat shock proteins, glucose regulated proteins, heme oxygenase-1) provide cellular protection through protein chaperone and/or anti-oxidative and anti-inflammatory functions. In recent years it has become clear that autophagy, a genetically-programmed and evolutionarily-conserved cellular process represents another adaptive response to cellular stress. During autophagy cytosolic material, including organelles, proteins, and foreign pathogens, are sequestered into membrane-bound vesicles termed autophagosomes, and then delivered to the lysosome for degradation. Through recycling of cellular biochemicals, autophagy provides a mechanism for adaptation to starvation. Recent research has uncovered selective autophagic pathways that target distinct cargoes to autophagosomes, including mechanisms for the clearance of aggregated protein, and for the removal of dysfunctional mitochondria (mitophagy). Autophagy can be induced by multiple forms of chemical and physical stress, including endoplasmic reticulum stress and oxidative stress, and plays an integral role in the mammalian stress response. Understanding of the interaction and co-regulation of autophagy with other stress-inducible systems will be useful in the design and implementation of therapeutics targeting this pathway.