Prohibitin 2 Is an Inner Mitochondrial Membrane Mitophagy Receptor
By Yongjie Wei, Wei-Chung Chiang, R. Sumpter, Prashant Mishra, Beth Levine. Cell, 2016
761 citations recorded by the source corpus.
SUMMARY 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 neurodegeneration and aging. However, the precise mechanisms of mitophagy remain uncertain. Here, we identify the inner mitochondrial membrane protein, prohibitin 2 (PHB2), as a crucial mitophagy receptor involved in targeting mitochondria for autophagic degradation. PHB2 binds the autophagosomal membrane-associated protein LC3 through an LC3-interaction region (LIR) domain upon mitochondrial 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 conserved mechanism of eukaryotic mitophagy and demonstrate a function of prohibitin 2 that may underlie its roles in physiology, aging, and disease.
Subfields: Cell Biology, Epidemiology, Molecular Biology
View Paper: https://www.semanticscholar.org/paper/a7fe001a5092a4104e3ad3d6714cf950a1224428
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Citations in the corpus
- Autophagy-Dependent Ferroptosis: Machinery and Regulation (2020, neutral): “, 2019), prohibitin 2 [PHB2] (Wei et al., 2017), two putative yeast Atg32 orthologs, BCL2 like 13 [BCL2L13] (Murakawa et al.”
- Mitochondria ROS and mitophagy in acute kidney injury (2022, background): “PHB2 (prohibitin 2), an IMM protein, binds the phagophore membrane-associated protein LC3 through a LIR domain which is required for PRKNinduced mitophagy in mammalian cells [54].”
- Molecular mechanisms and physiological functions of mitophagy (2021, neutral): “The IMM protein prohibitin 2 also plays a role in the selective engulfment of paternal mitochondria by autophagosomes and functions as an autophagy receptor for damaged mitochondria in mammals and paternal mitochondria in C. elegans (Wei et al , 2017).”
- Molecular definitions of autophagy and related processes (2017, neutral): “…to allow recognition by sequestosome 1 (SQSTM1, best known as p62) (to a limited extent), optineurin (OPTN), calcium binding and coiled-coil domain 2 (CALCOCO2; best known as NDP52), and LC3 (Wong & Holzbaur, 2014; Heo et al , 2015; Lazarou et al , 2015; Moore & Holzbaur, 2016; Wei et al , 2017).”
- The mitophagy pathway and its implications in human diseases (2023, background): “146 ,147 PHB2: PHB2 is an IMM mitophagy receptor that binds to PHB/ PHB1 to form an alternating tetrameric new gene (RING)- fi nger domain ‐ like complex (Fig.”