Mitophagy is the selective autophagy of damaged mitochondria, essential for maintaining cellular energy homeostasis and preventing cell death. It plays critical roles in various physiological and pathological processes, including red blood cell differentiation, paternal mitochondrial degradation, neurodegenerative diseases, and tissue injury. Mitophagy involves two steps: induction of general autophagy and priming of damaged mitochondria for selective autophagic recognition. Recent studies have identified key pathways, such as the Pink1-Parkin signaling pathway and mitophagic receptors like Nix and Bnip3, that regulate mitophagy. In yeast, Atg32 is a mitochondrial receptor for mitophagy, while in mammals, Nix and Bnip3 are involved in mitochondrial clearance. Mitophagy is also regulated by mitochondrial fragmentation, which facilitates the recognition of damaged mitochondria by autophagy machinery. The Pink1-Parkin pathway is crucial for mitochondrial quality control, with Pink1 stabilizing Parkin on depolarized mitochondria, leading to Parkin-mediated ubiquitination and subsequent mitophagy. Other factors, such as FUNDC1, ULK1, and the Hsp90-Cdc37 complex, also play roles in mitophagy. Mitophagy is involved in various pathophysiological conditions, including aging, cancer, and neurodegenerative diseases, where it helps maintain mitochondrial function and prevent cellular damage. Understanding mitophagy mechanisms is essential for developing therapeutic strategies for these conditions.Mitophagy is the selective autophagy of damaged mitochondria, essential for maintaining cellular energy homeostasis and preventing cell death. It plays critical roles in various physiological and pathological processes, including red blood cell differentiation, paternal mitochondrial degradation, neurodegenerative diseases, and tissue injury. Mitophagy involves two steps: induction of general autophagy and priming of damaged mitochondria for selective autophagic recognition. Recent studies have identified key pathways, such as the Pink1-Parkin signaling pathway and mitophagic receptors like Nix and Bnip3, that regulate mitophagy. In yeast, Atg32 is a mitochondrial receptor for mitophagy, while in mammals, Nix and Bnip3 are involved in mitochondrial clearance. Mitophagy is also regulated by mitochondrial fragmentation, which facilitates the recognition of damaged mitochondria by autophagy machinery. The Pink1-Parkin pathway is crucial for mitochondrial quality control, with Pink1 stabilizing Parkin on depolarized mitochondria, leading to Parkin-mediated ubiquitination and subsequent mitophagy. Other factors, such as FUNDC1, ULK1, and the Hsp90-Cdc37 complex, also play roles in mitophagy. Mitophagy is involved in various pathophysiological conditions, including aging, cancer, and neurodegenerative diseases, where it helps maintain mitochondrial function and prevent cellular damage. Understanding mitophagy mechanisms is essential for developing therapeutic strategies for these conditions.