Amity Institute of Biotechnology, Amity University, Kolkata, Plot No: 36, 37 & 38, Major Arterial Road, Action Area II, Kadampukur Village, Newtown, Kolkata, West Bengal, 700135, India.
Division of Infectious Diseases and Immunology, CSIR-Indian Institute of Chemical Biology, 4 Raja S.C. Mullick Road, Kolkata, West Bengal, 700032, India.
Cell Biol Toxicol. 2021 Jun;37(3):333-366. doi: 10.1007/s10565-020-09561-1. Epub 2020 Oct 17.
Mitochondria are double membrane-bound cellular work-horses constantly functioning to regulate vital aspects of cellular metabolism, bioenergetics, proliferation and death. Biogenesis, homeostasis and regulated turnover of mitochondria are stringently regulated to meet the bioenergetic requirements. Diverse external and internal stimuli including oxidative stress, diseases, xenobiotics and even age profoundly affect mitochondrial integrity. Damaged mitochondria need immediate segregation and selective culling to maintain physiological homeostasis. Mitophagy is a specialised form of macroautophagy that constantly checks mitochondrial quality followed by elimination of rogue mitochondria by lysosomal targeting through multiple pathways tightly regulated and activated in context-specific manners. Mitophagy is implicated in diverse oxidative stress-associated metabolic, proliferating and degenerative disorders owing to the centrality of mitopathology in diseases as well as the common mandate to eliminate damaged mitochondria for restoring physiological homeostasis. With improved health care and growing demand for precision medicine, specifically targeting the keystone factors in pathogenesis, more exploratory studies are focused on mitochondrial quality control as underlying guardian of cellular pathophysiology. In this context, mitophagy emerged as a promising area to focus biomedical research for identifying novel therapeutic targets against diseases linked with physiological redox perturbation. The present review provides a comprehensive account of the recent developments on mitophagy along with precise discussion on its impact on major diseases and possibilities of therapeutic modulation.
线粒体是双层膜结合的细胞“工作马”，不断调节细胞代谢、生物能量学、增殖和死亡的重要方面。线粒体的生物发生、动态平衡和有调节的周转受到严格的调控，以满足生物能量学的需求。包括氧化应激、疾病、外源性化学物质甚至年龄在内的各种外部和内部刺激都会深刻影响线粒体的完整性。受损的线粒体需要立即进行隔离和选择性清除，以维持生理动态平衡。自噬是一种特殊的巨自噬形式，它通过多种途径不断检查线粒体的质量，然后通过溶酶体靶向将有缺陷的线粒体进行选择性清除，这些途径受到严格的调控，并以特定的方式激活。由于线粒体病理学在疾病中的中心地位以及消除受损线粒体以恢复生理动态平衡的共同要求，自噬与多种与氧化应激相关的代谢、增殖和退行性疾病有关。随着医疗保健的改善和对精准医学的需求不断增长，特别是针对发病机制中的关键因素，更多的探索性研究集中在作为细胞病理生理学基础的线粒体质量控制上。在这种情况下，自噬作为一个有前途的研究领域，成为确定与生理氧化还原失调相关疾病的新治疗靶点的生物医学研究的重点。本综述提供了自噬的最新研究进展的全面概述，并详细讨论了其对主要疾病的影响以及治疗调节的可能性。
