Full metadata record
DC Field | Value | Language |
---|---|---|
dc.contributor.author | 고현철 | - |
dc.date.accessioned | 2019-12-07T11:14:07Z | - |
dc.date.available | 2019-12-07T11:14:07Z | - |
dc.date.issued | 2018-03 | - |
dc.identifier.citation | TOXICOLOGY LETTERS, v. 284, page. 120-128 | en_US |
dc.identifier.issn | 0378-4274 | - |
dc.identifier.issn | 1879-3169 | - |
dc.identifier.uri | https://www.sciencedirect.com/science/article/pii/S037842741731514X?via%3Dihub | - |
dc.identifier.uri | https://repository.hanyang.ac.kr/handle/20.500.11754/118020 | - |
dc.description.abstract | Mitochondrial dynamics and mitophagy are critical processes for regulating mitochondrial homeostasis. Phosphoglycerate mutase family member 5 (PGAM5) is a mitochondrial protein that plays crucial roles in apoptosis and necroptosis, but the roles of PGAM5 in mitochondrial dynamics and mitophagy remain unclear. In this study, we investigated the role of PGAM5 in carbonyl cyanide m-chlorophenylhydrazone (CCCP)-induced mitochondrial damage and the correlation between mitochondrial dynamics and mitophagy using SH-SY5Y cells. We found that CCCP decreased mitochondrial membrane potential, resulting in mitochondrial dysfunction. CCCP increased PGAM5, dynamin-related protein 1 (DRP1), and optic atrophy 1 (OPA1) expression of the mitochondrial fraction in a time-dependent manner. Knockdown of PGAM5 inhibited DRP1 translocation without a change in OPA1 expression in CCCP-treated cells. Furthermore, knockdown of PGAM5 and DRP1 significantly blocked the increase of PTEN-induced putative protein kinase 1 (PINK1) and Parkin expression in the mitochondrial fraction of CCCP-treated cells. Interestingly, CCCP did not alter PINK1/Parkin expression in the mitochondrial fraction of OPA1 knockdown cells. Inhibiting mitophagy by PGAM5 knockdown accelerated CCCP-induced apoptosis. CCCP treatment also results in PINK1 stabilization on the mitochondrial membrane, which subsequently increases Parkin recruitment from the cytosol to abnormal mitochondria. In addition, we found that CCCP increased the level of mitochondrial LC3II, indicating that Parkin recruitment of PINK1 is a result of mitophagy. We propose that activation of PGAM5 is associated with DRP1 recruitment and PINK1 stabilization, which contribute to the modulation of mitophagy in CCCP-treated cells with mitochondrial dysfunction. In conclusion, we demonstrated that PGAM5 regulates PINK1-Parkin-mediated mitophagy, which can exert a neuroprotective effect against CCCP-induced apoptosis. | en_US |
dc.description.sponsorship | This work was supported by the Korea Science and Engineering Foundation (2017R1A5A2015395) through the Medical Research Center at Hanyang University College of Medicine, Republic of Korea, and by the Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education, Science and Technology (2015R1D1A1A01059531). | en_US |
dc.language.iso | en_US | en_US |
dc.publisher | ELSEVIER IRELAND LTD | en_US |
dc.subject | CCCP | en_US |
dc.subject | PGAM5 | en_US |
dc.subject | DRP1 | en_US |
dc.subject | PINK1 | en_US |
dc.subject | Mitophagy | en_US |
dc.subject | Mitochondrial dynamics | en_US |
dc.title | PGAM5 regulates PINK1/Parkin-mediated mitophagy via DRP1 in CCCP-induced mitochondrial dysfunction | en_US |
dc.type | Article | en_US |
dc.relation.volume | 284 | - |
dc.identifier.doi | 10.1016/j.toxlet.2017.12.004 | - |
dc.relation.page | 120-128 | - |
dc.relation.journal | TOXICOLOGY LETTERS | - |
dc.contributor.googleauthor | Park, Yun Sun | - |
dc.contributor.googleauthor | Choi, Su Eun | - |
dc.contributor.googleauthor | Koh, Hyun Chul | - |
dc.relation.code | 2018001407 | - |
dc.sector.campus | S | - |
dc.sector.daehak | COLLEGE OF MEDICINE[S] | - |
dc.sector.department | DEPARTMENT OF MEDICINE | - |
dc.identifier.pid | hckoh | - |
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