Levine Beth, Klionsky Daniel J
Center for Autophagy Research, Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX 75390;
Department of Microbiology, University of Texas Southwestern Medical Center, Dallas, TX 75390.
Proc Natl Acad Sci U S A. 2017 Jan 10;114(2):201-205. doi: 10.1073/pnas.1619876114. Epub 2016 Dec 30.
Autophagy is an ancient pathway in which parts of eukaryotic cells are self-digested within the lysosome or vacuole. This process has been studied for the past seven decades; however, we are only beginning to gain a molecular understanding of the key steps required for autophagy. Originally characterized as a hormonal and starvation response, we now know that autophagy has a much broader role in biology, including organellar remodeling, protein and organelle quality control, prevention of genotoxic stress, tumor suppression, pathogen elimination, regulation of immunity and inflammation, maternal DNA inheritance, metabolism, and cellular survival. Although autophagy is usually a degradative pathway, it also participates in biosynthetic and secretory processes. Given that autophagy has a fundamental role in many essential cellular functions, it is not surprising that autophagic dysfunction is associated with a wide range of human diseases. Genetic studies in various fungi, particularly Saccharomyces cerevisiae, provided the key initial breakthrough that led to an explosion of research on the basic mechanisms and the physiological connections of autophagy to health and disease. The Nobel Committee has recognized this breakthrough by the awarding of the 2016 Nobel Prize in Physiology or Medicine for research in autophagy.
自噬是一种古老的细胞途径，真核细胞的部分成分会在溶酶体或液泡内进行自我消化。在过去的七十年里，这一过程一直受到研究；然而，我们才刚刚开始从分子层面理解自噬所需的关键步骤。自噬最初被认为是一种对激素和饥饿的反应，现在我们知道它在生物学中具有更广泛的作用，包括细胞器重塑、蛋白质和细胞器质量控制、预防基因毒性应激、肿瘤抑制、病原体清除、免疫和炎症调节、母系DNA遗传、新陈代谢以及细胞存活。尽管自噬通常是一种降解途径，但它也参与生物合成和分泌过程。鉴于自噬在许多基本细胞功能中起着基础性作用，自噬功能障碍与多种人类疾病相关也就不足为奇了。对各种真菌，特别是酿酒酵母的遗传学研究提供了关键的初步突破，引发了对自噬基本机制以及自噬与健康和疾病生理联系的研究热潮。诺贝尔委员会通过授予2016年诺贝尔生理学或医学奖来认可这一突破，该奖项授予了在自噬研究方面的成果。
