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Fig. 2 | Cell Communication and Signaling

Fig. 2

From: The role of mitophagy in innate immune responses triggered by mitochondrial stress

Fig. 2

Molecular mechanisms of mitophagy. Ub-dependent mitophagy usually refers to Pink1-Parkin-mediated mitophagy. Upon mitochondrial depolarization, full-length Pink1 accumulates on the OMM and recruits Parkin to the mitochondrial surface. Pink1 triggers Parkin E3 ligase activity through a circuit of modifications including phosphorylation of both Parkin and ubiquitin. Then, parkin ubiquitinates various OMM proteins including VDAC1 and MFN1/2. Polyubiquitinated proteins can be recognized by several adaptor molecules, including p62, OPTN and NDP52. These proteins interact with lipidated LC3 via the LIR motif to promote the encapsulation of damaged mitochondria by the autophagosome. In addition, deubiquitinase such as USP8, USP15, USP30, USP35 can cause the deubiquitination of Parkin and OMM proteins. Ub-independent mitophagy depends on several LIR containing mitophagy receptors, including FUNDC1, BNIP3, NIX, BCL2L13, FKBP8 and NLRX1. Besides, IMM proteins (such as cardiolipin and PHB2) interact with lipidated LC3 through the LIR motif, thereby promoting the phagocytosis of defective mitochondria. Overall, mitophagy adaptors and receptors bind to LC3 bound on the phagophores for further expansion and closure to form mitophagosomes, subsequently, mitophagosomes fuse with lysosomes form autolysosome for mitochondrial degradation

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