Fig. 1: The mechanism of mitophagy.
From: Mitophagy in ischemic heart disease: molecular mechanisms and clinical management

Mitophagy can be divided into approximately four key steps: 1. In the early stage of mitochondrial damage, permeability transition occurs, leading to mitochondrial depolarization, loss of membrane potential, and induction of mitochondrial autocorrelation protein activation. 2. In the early stage, autophagosomes wrap around damaged mitochondria, forming mitophagy. 3. In the middle stage, mitochondrial autophagosomes fuse with lysosomes to form mature mitochondrial autophagosomes. 4. Lysosomal acidic hydrolytic enzymes flow into autophagosomes to degrade mitochondria, allowing nutrients to be recycled and reused. The molecular mechanism of mitophagy can be mainly divided into ubiquitin dependent pathway and non ubiquitin dependent pathway. The key proteins in the ubiquitin dependent pathway are PINK1 and Parkin. In addition, besides the PINK1 Parkin pathway, there is also a non Parkin dependent ubiquitin dependent pathway. That is to say, PINK1 can also recruit self receptor proteins (such as NIX, BNIP3, and FUNDC1) directly to mitochondria through ubiquitin phosphorylation, and the receptor proteins recruit LC3, which enables the self to engulf mitochondria. Non ubiquitin dependent mitophagy is dominated by mitophagy receptors, which differs significantly from the ubiquitin dependent pathway.