Department of Pharmacology and Toxicology, College of Pharmacy, University of Arizona, Tucson, AZ 85724, USA.
J Appl Toxicol. 2012 Jul;32(7):465-79. doi: 10.1002/jat.1787. Epub 2012 Feb 15.
Autophagy is a critical cellular process orchestrating the lysosomal degradation of cellular components in order to maintain cellular homeostasis and respond to cellular stress. A growing research effort over the last decade has proven autophagy to be essential for constitutive protein and organelle turnover, for embryonic/neonatal survival and for cell survival during conditions of environmental stress. Emphasizing its biological importance, dysfunctional autophagy contributes to a diverse set of human diseases. Cellular stress induced by xenobiotic exposure typifies environmental stress, and can result in the induction of autophagy as a cytoprotective mechanism. An increasing number of xenobiotics are notable for their ability to modulate the induction or the rate of autophagy. The role of autophagy in normal cellular homeostasis, the intricate relationship between cellular stress and the induction of autophagy, and the identification of specific xenobiotics capable of modulating autophagy, point to the importance of the autophagic process in toxicology. This review will summarize the importance of autophagy and its role in cellular response to stress, including examples in which consideration of autophagy has contributed to a more complete understanding of toxicant-perturbed systems.
自噬是一个关键的细胞过程，协调溶酶体降解细胞成分，以维持细胞内环境平衡并响应细胞应激。在过去十年中，越来越多的研究证明自噬对于组成性蛋白质和细胞器的周转、胚胎/新生儿的存活以及环境应激条件下细胞的存活都是必不可少的。强调其生物学重要性，功能失调的自噬导致了一系列人类疾病。外源性物质暴露引起的细胞应激是环境应激的典型代表，可诱导自噬作为一种细胞保护机制。越来越多的外源性物质因其调节自噬的诱导或速率的能力而引人注目。自噬在正常细胞内环境平衡中的作用、细胞应激与自噬诱导之间的复杂关系，以及能够调节自噬的特定外源性物质的鉴定，都表明自噬过程在毒理学中的重要性。这篇综述将总结自噬的重要性及其在细胞对应激的反应中的作用，包括在这些例子中，考虑自噬有助于更全面地理解毒物扰乱的系统。
