Petibone Dayton M, Majeed Waqar, Casciano Daniel A
National Center for Toxicological Research, US FDA, Division of Genetic and Molecular Toxicology, Jefferson, AR, 72079, USA.
Center of Integrative Nanotechnology Sciences, University of Arkansas at Little Rock, Little Rock, AR, 72204, USA.
J Appl Toxicol. 2017 Jan;37(1):23-37. doi: 10.1002/jat.3393. Epub 2016 Sep 29.
Autophagy is a cellular process that facilitates nutrient turnover and removal of expended macromolecules and organelles to maintain homeostasis. The recycling of cytosolic macromolecules and damaged organelles by autophagosomes occurs through the lysosomal degradation pathway. Autophagy can also be upregulated as a prosurvival pathway in response to stress stimuli such as starvation, hypoxia or cell damage. Over the last two decades, there has been a surge in research revealing the basic molecular mechanisms of autophagy in mammalian cells. A corollary of an advanced understanding of autophagy has been a concurrent expansion of research into understanding autophagic function and dysfunction in pathology. Recent studies have revealed a pivotal role for autophagy in drug toxicity, and for utilizing autophagic components as diagnostic markers and therapeutic targets in treating disease and cancer. In this review, advances in understanding the molecular basis of mammalian autophagy, methods used to induce and evaluate autophagy, and the diverse interactions between autophagy and drug toxicity, disease progression and carcinogenesis are discussed. Copyright © 2016 John Wiley & Sons, Ltd.
自噬是一种细胞过程，可促进营养物质周转以及清除消耗的大分子和细胞器，以维持体内稳态。自噬体对胞质大分子和受损细胞器的循环利用通过溶酶体降解途径进行。自噬也可作为一种促生存途径被上调，以响应饥饿、缺氧或细胞损伤等应激刺激。在过去二十年中，揭示哺乳动物细胞自噬基本分子机制的研究激增。对自噬的深入理解的一个必然结果是，同时展开了对自噬在病理学中的功能及功能障碍的研究。最近的研究揭示了自噬在药物毒性中的关键作用，以及在将自噬成分用作疾病和癌症治疗中的诊断标志物和治疗靶点方面的作用。在这篇综述中，我们讨论了在理解哺乳动物自噬分子基础方面取得的进展、用于诱导和评估自噬的方法，以及自噬与药物毒性、疾病进展和致癌作用之间的各种相互作用。版权所有© 2016约翰威立父子有限公司。
