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Fig. 1. Adaptor protein-mediated mitophagy is dependent on the PINK1/Parkin pathway. In damaged mitochondria that have lost their mitochondrial membrane potential (ΔΨm), PINK1 accumulates and phosphorylates ubiquitin, which recruits the E3 ligase Parkin. Parkin ubiquitinates outer mitochondrial membrane (OMM) proteins such as Mfn1/2, MIRO, and VDAC. The poly-ubiquitinated proteins serve as binding sites for selective autophagy adaptors including OPTN, p62, NDP52, TAX1BP1, and NBR1. These proteins contain LC3-binding sites (LIR), leading to the encapsulation of mitochondria by the autophagosome. TBK1 phosphorylates OPTN, thereby enhancing its binding ability. Receptor-mediated mitophagy relies on other OMM proteins, including BNIP3, NIX, and FUNDC1. In addition, inner mitochondrial membrane proteins, such as PHB2 and cardiolipin, function as receptors in the response to mitochondrial damage.
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