Autophagy Inflammation and Metabolism Center of Biomedical Research Excellence, University of New Mexico Health Sciences Center, Albuquerque, NM, USA.
Department of Molecular Genetics and Microbiology, University of New Mexico Health Sciences Center, Albuquerque, NM, USA.
Autophagy. 2022 Feb;18(2):283-292. doi: 10.1080/15548627.2021.1933742. Epub 2021 Jun 22.
The autophagy, macroautophagy, is considered to be both a metabolic process as well as a bona fide quality control process. The question as to how these two aspects of autophagy are coordinated and whether and why they overlap has implications for fundamental aspects, pathophysiological effects, and pharmacological manipulation of autophagy. At the top of the regulatory cascade controlling autophagy are master regulators of cellular metabolism, such as MTOR and AMPK, which render the system responsive to amino acid and glucose starvation. At the other end exists a variety of specific autophagy receptors, engaged in the selective removal of a diverse array of intracellular targets, from protein aggregates/condensates to whole organelles such as mitochondria, ER, peroxisomes, lysosomes and lipid droplets. Are the roles of autophagy in metabolism and quality control mutually exclusive, independent or interlocked? How are priorities established? What are the molecular links between both phenomena? This article will provide a starting point to formulate these questions, the responses to which should be taken into consideration in future autophagy-based interventions.
自噬，即巨自噬，被认为既是一种代谢过程，也是一种真正的质量控制过程。自噬的这两个方面如何协调，以及它们是否重叠以及为什么重叠，这对自噬的基础方面、病理生理效应和药理学干预都有影响。调控自噬的调控级联的顶端是细胞代谢的主调控因子，如 MTOR 和 AMPK，它们使系统对氨基酸和葡萄糖饥饿有反应。在另一端存在着各种特定的自噬受体，参与选择性地去除各种细胞内靶标，从蛋白质聚集体/凝聚物到整个细胞器，如线粒体、内质网、过氧化物酶体、溶酶体和脂滴。自噬在代谢和质量控制中的作用是相互排斥的、独立的还是相互关联的？优先级如何确定？这两种现象之间有什么分子联系？本文将为这些问题提供一个起点，在未来基于自噬的干预中应该考虑到对这些问题的回应。
