FUNDC1 regulates receptor-mediated mitophagy independently of the PINK1/Parkin-dependent pathway in rotenone-treated SH-SY5Y cells
- Title
- FUNDC1 regulates receptor-mediated mitophagy independently of the PINK1/Parkin-dependent pathway in rotenone-treated SH-SY5Y cells
- Author
- 고현철
- Keywords
- FUNDC1; PINK1/Parkin; Mitophagy; Mitochondrial dynamics; Rotenone
- Issue Date
- 2020-03
- Publisher
- PERGAMON-ELSEVIER SCIENCE LTD
- Citation
- FOOD AND CHEMICAL TOXICOLOGY, v. 137, article no. 111163
- Abstract
- Upon mitochondrial stress, PINK1 and Parkin cooperatively mediate a response that removes damaged mitochondria. In addition to the PINK1/Parkin pathway, the FUNDC1, mitophagy receptor regulates mitochondrial clearance. It is not clear whether these systems coordinate to mediate mitophagy in response to stress. Rotenone caused an increase in LC3H expression, and FUNDC1-knocked down cells showed remarkably reduced LC3 expression compared to control cells. In addition, treatment of cells with autophagy flux inhibitor, chloroquine, induced further accumulation of LC3-II, suggesting that mitophagy induced by rotenone is due to involvement of mitochondrial FUNDC1. Rotenone treatment resulted in PINK1 stabilization on the outer mitochondrial membrane and a subsequent increase in recruitment of Parkin from the cytosol to the abnormal mitochondria, as well as physical interaction of PINK1 with Parkin in the mitochondria of rotenone-treated cells. Interestingly, knockdown of FUNDC1 did not alter PINK1/Parkin expression in the mitochondrial fraction of rotenone-treated cells. Our findings indicate that FUNDC1 involves in receptor-mediated mitophagy separately from PINK1/ Parkin-dependent mitophagy. Furthermore, inhibiting mitophagy by FUNDC1 or PINK1 knockdown accelerated rotenone-induced cytotoxicity. Taken together, our findings suggest that rotenone can be induced both receptormediated and PINK1/Parkin-dependent mitophagy for mitochondrial clearance, and that mitophagy by removing damaged mitochondria, has cytoprotective effects.
- URI
- https://www.sciencedirect.com/science/article/pii/S027869152030051X?via%3Dihubhttps://repository.hanyang.ac.kr/handle/20.500.11754/162672
- ISSN
- 0278-6915; 1873-6351
- DOI
- 10.1016/j.fct.2020.111163
- Appears in Collections:
- COLLEGE OF MEDICINE[S](의과대학) > MEDICINE(의학과) > Articles
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