Lysosomal Ca2+-mediated TFEB activation modulates mitophagy and functional adaptation of pancreatic beta-cells to metabolic stress
DC Field | Value | Language |
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dc.contributor.author | Park, Kihyoun | - |
dc.contributor.author | Lim, Hyejin | - |
dc.contributor.author | Kim, Jinyoung | - |
dc.contributor.author | Hwang, Yeseong | - |
dc.contributor.author | Lee, Yu Seol | - |
dc.contributor.author | Bae, Soo Han | - |
dc.contributor.author | Kim, Hyeongseok | - |
dc.contributor.author | Kim, Hail | - |
dc.contributor.author | Kang, Shin-Wook | - |
dc.contributor.author | Kim, Joo Young | - |
dc.contributor.author | Lee, Myung-Shik | - |
dc.date.accessioned | 2022-05-24T01:49:53Z | - |
dc.date.available | 2022-05-24T01:49:53Z | - |
dc.date.issued | 2022-03 | - |
dc.identifier.issn | 2041-1723 | - |
dc.identifier.issn | 2041-1723 | - |
dc.identifier.uri | https://scholarworks.bwise.kr/sch/handle/2021.sw.sch/20762 | - |
dc.description.abstract | Although autophagy is critical for pancreatic beta-cell function, the role and mechanism of mitophagy in beta-cells are unclear. We studied the role of lysosomal Ca2+ in TFEB activation by mitochondrial or metabolic stress and that of TFEB-mediated mitophagy in beta-cell function. Mitochondrial or metabolic stress induced mitophagy through lysosomal Ca2+ release, increased cytosolic Ca2+ and TFEB activation. Lysosomal Ca2+ replenishment by ER- > lysosome Ca2+ refilling was essential for mitophagy. beta-cell-specific Tfeb knockout (Tfeb(Delta beta-cell)) abrogated high-fat diet (HFD)-induced mitophagy, accompanied by increased ROS and reduced mitochondrial cytochrome c oxidase activity or O-2 consumption. Tfeb(Delta beta-cell) mice showed aggravation of HFD-induced glucose intolerance and impaired insulin release. Metabolic or mitochondrial stress induced TFEB-dependent expression of mitophagy receptors including Ndp52 and Optn, contributing to the increased mitophagy. These results suggest crucial roles of lysosomal Ca2+ release coupled with ER- > lysosome Ca2+ refilling and TFEB activation in mitophagy and maintenance of pancreatic beta-cell function during metabolic stress. Autophagy is important for pancreatic beta-cell function, however, the role of mitophagy and mechanism for mitophagy in beta-cells are unclear. Here the authors report that in stressed beta-cells, lysosomal Ca2+ release promotes mitophagy via activation of the transcription factor EB (TFEB) and loss of beta-cell TFEB aggravates glucose intolerance during high-fat diet. | - |
dc.format.extent | 17 | - |
dc.language | 영어 | - |
dc.language.iso | ENG | - |
dc.publisher | Nature Publishing Group | - |
dc.title | Lysosomal Ca2+-mediated TFEB activation modulates mitophagy and functional adaptation of pancreatic beta-cells to metabolic stress | - |
dc.type | Article | - |
dc.publisher.location | 영국 | - |
dc.identifier.doi | 10.1038/s41467-022-28874-9 | - |
dc.identifier.scopusid | 2-s2.0-85126228121 | - |
dc.identifier.wosid | 000769063600017 | - |
dc.identifier.bibliographicCitation | Nature Communications, v.13, no.1, pp 1 - 17 | - |
dc.citation.title | Nature Communications | - |
dc.citation.volume | 13 | - |
dc.citation.number | 1 | - |
dc.citation.startPage | 1 | - |
dc.citation.endPage | 17 | - |
dc.type.docType | Article | - |
dc.description.isOpenAccess | Y | - |
dc.description.journalRegisteredClass | scie | - |
dc.description.journalRegisteredClass | scopus | - |
dc.relation.journalResearchArea | Science & Technology - Other Topics | - |
dc.relation.journalWebOfScienceCategory | Multidisciplinary Sciences | - |
dc.subject.keywordPlus | TRANSCRIPTION FACTORS | - |
dc.subject.keywordPlus | INSULIN-RESISTANCE | - |
dc.subject.keywordPlus | SKELETAL-MUSCLE | - |
dc.subject.keywordPlus | CA2+ CHANNELS | - |
dc.subject.keywordPlus | AUTOPHAGY | - |
dc.subject.keywordPlus | INHIBITION | - |
dc.subject.keywordPlus | CALCINEURIN | - |
dc.subject.keywordPlus | HOMEOSTASIS | - |
dc.subject.keywordPlus | BIOGENESIS | - |
dc.subject.keywordPlus | REVEALS | - |
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