Mitophagy and Its Contribution to Metabolic and Aging-Associated Disorders.

Abstract

Significance: Mitochondria are the cellular powerhouses for ATP synthesis through oxidative phosphorylation, and the centers for fatty acid β-oxidation, metabolite synthesis, reactive oxygen species production, innate immunity, and apoptosis. To fulfill these critical functions, mitochondrial quality and homeostasis must be well maintained. Abnormal mitochondrial quality contributes to aging and age-related disorders, such as metabolic syndrome, cancers, and neurodegenerative diseases. Recent Advances: Mitophagy is a cellular process that selectively removes damaged or superfluous mitochondria by autolysosomal degradation and is regarded as one of the major mechanisms responsible for mitochondrial quality control. Critical Issues: To date, distinct mitophagy pathways have been discovered, including receptor-mediated mitophagy and ubiquitin-dependent mitophagy. Emerging knowledge of these pathways shows that they play important roles in sensing mitochondrial stress and signaling for metabolic adaptations. Future Directions: Here, we provide a review on the molecular mechanisms for mitophagy and its interplay with cellular metabolism, with a particular focus on its role in metabolic and age-related disorders.