Journal
CELL BIOLOGY AND TOXICOLOGY
Volume 37, Issue 3, Pages 333-366Publisher
SPRINGER
DOI: 10.1007/s10565-020-09561-1
Keywords
Mitochondrial quality control; Mitophagy; Autophagy; Oxidative stress; Mitochondrial apoptosis; Mitochondrial disease
Categories
Funding
- Science and Engineering Research Board, Dept. of Science and Technology, Ministry of Science and Technology [SB/S2/JCB-54/2014]
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Mitochondria play crucial roles in cellular metabolism, bioenergetics, proliferation, and death, and their quality is influenced by various external and internal stimuli. Mitophagy is essential for quality control and selective elimination of damaged mitochondria to maintain physiological homeostasis.
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.
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