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. 2022 Nov 12;298(12):102704. doi: 10.1016/j.jbc.2022.102704

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© 2022 The Authors

This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).

PMC Copyright notice

Schematic model illustrating the contribution of Parkin-mediated IMM PHB2 ubiquitination to efficient mitophagy. Step 1: upon mitochondrial damage, PINK1 accumulates on mitochondrion to phosphorylate ubiquitin and Parkin, and then OMM proteins are ubiquitinated by Parkin. Step 2: ubiquitinated OMM proteins are degraded by proteasomes, leading to OMM rupture (melting). Step 3: Parkin promotes ubiquitination of IMM protein PHB2 on K142/K200 sites, thereby promoting the association between PHB2 and LC3-labeled autophagosome, possibly due to the conformational change of PHB2. Step 4: the entire mitochondrion is degraded by autophagy-lysosome pathway. IMM, inner mitochondrial membrane; OMM, outer mitochondrial membrane; PHB2, prohibitin 2.