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PHB2 interacts with LC3 and SQSTM1 is required for bile acids-induced mitophagy in cholestatic liver.
- Source :
-
Cell death & disease [Cell Death Dis] 2018 Feb 07; Vol. 9 (2), pp. 160. Date of Electronic Publication: 2018 Feb 07. - Publication Year :
- 2018
-
Abstract
- Mitophagy is a major pathway for clearance of injured mitochondria. However, whether mitophagy is involved in the cholestasis-induced damages of hepatic mitochondria remains unknown. We here aimed to investigate the molecular links between cholestasis and hepatic mitophagy. We show that mitophagy is increased significantly in livers of biliary atresia (BA) that is cholestatic disease in infants. The mitochondrial-toxicity bile acids treatment increases the activities of mitophagy in hepatocytes. Mechanistically, we find that the prohibitin 2 (PHB2) is crucial for cholestasis-mediated mitophagy in vitro. On the one hand, PHB2 binds the autophagosomal membrane-associated protein LC3 upon injured mitochondria via an LC3-interaction region domain. On the other hand, PHB2 forms a ternary protein complex with sequestosome 1 (SQSTM1) and LC3, leading to loading of LC3 onto the damaged mitochondria. Altogether, our study suggests that PHB2 is required for cholestasis-induced mitophagy via LC3 onto the injured mitochondria.
- Subjects :
- Cell Line
Cholestasis pathology
Humans
Infant
Liver ultrastructure
Mitochondria metabolism
Prohibitins
Protein Binding
Bile Acids and Salts metabolism
Cholestasis metabolism
Liver metabolism
Liver pathology
Microtubule-Associated Proteins metabolism
Mitophagy
Repressor Proteins metabolism
Sequestosome-1 Protein metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 2041-4889
- Volume :
- 9
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- Cell death & disease
- Publication Type :
- Academic Journal
- Accession number :
- 29416008
- Full Text :
- https://doi.org/10.1038/s41419-017-0228-8