Mitochondrial priming in mitophagy.

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Mitochondrial priming in mitophagy. Mitochondrial priming in mitophagy. PINK1 accumulation on the outer mitochondrial membrane recruits Parkin to the mitochondria. In addition, BNIP3 and BNIP3L on the OMM also recruit Parkin to the mitochondria. In turn, Parkin will ubiquitinate mitochondrial proteins, such as VDAC1. Ubiquitinated proteins are recognized by p62, which interacts with LC3 on autophagosomes. In addition, BNIP3 and BNIP3L also interact with the autophagosomal protein LC3, thereby inducing association with the autophagosomal membrane. The increase in ROS production induced by BNIP3 and BNIP3L via the depolarization of ΔΨm will inhibit mTORC1 activity. In addition, the inactivation of Rheb by BNIP3 and BNIP3L will inhibit mTORC1 activity. MM, mitochondrial matrix; IMM, inner mitochondrial membrane; IMS, intermembrane space; OMM, outer mitochondrial membrane; ROS, reactive oxygen species. Marlous J. Groenewoud, and Fried J. T. Zwartkruis Open Biol. 2013;3:130185