Prohibitin 2 Is an Inner Mitochondrial Membrane Mitophagy Receptor

The removal of unwanted or damaged mitochondria by autophagy, a process called mitophagy, is essential for key events in development, cellular homeostasis, tumor suppression, and prevention of neuro-degeneration and aging. However, the precise mechanisms of mitophagy remain uncertain. Here, we identify the inner mitochondrialmembrane protein, prohibitin 2 (PHB2), as a crucial mitophagy receptor involved in targeting mitochondria for autophagic degradation. PHB2 binds the autophagosomal membrane- associatedprotein LC3 through an LC3-interaction region (LIR) domain uponmitochondrial depolarization and proteasome-dependent outer membrane rupture. PHB2 is required for Parkin-induced mitophagy in mammalian cells and for the clearance of paternal mitochondria after embryonic fertilization in C. elegans. Our findings pinpoint a conservedmechanism of eukaryotic mitophagy and demonstrate a function of prohibitin 2 that may underlie its roles in physiology, aging, and disease.