Essential role of lysosomal Ca2+-mediated TFEB activation in mitophagy and functional adaptation of pancreatic β-cells to metabolic stress
DC Field | Value | Language |
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dc.contributor.author | Park, Kihyoun | - |
dc.contributor.author | Lee, Myung-Shik | - |
dc.date.accessioned | 2022-11-29T02:40:58Z | - |
dc.date.available | 2022-11-29T02:40:58Z | - |
dc.date.issued | 2022-12 | - |
dc.identifier.issn | 1554-8627 | - |
dc.identifier.issn | 1554-8635 | - |
dc.identifier.uri | https://scholarworks.bwise.kr/sch/handle/2021.sw.sch/21706 | - |
dc.description.abstract | Although the role of pancreatic beta-cell macroautophagy/autophagy is well known, that of beta-cell mitophagy is unclear. We investigated the changes of lysosomal Ca2+ by mitochondrial or metabolic stress that can modulate TFEB activation and, additionally, the role of TFEB-induced mitophagy in beta-cell function. Mitochondrial or metabolic stress induces mitophagy, which is mediated by lysosomal Ca2+ release, increased cytosolic [Ca2+] and subsequent TFEB activation. Lysosomal Ca2+ release is replenished by ER -> lysosome Ca2+ refilling through ER Ca2+ exit channels, which is important for the increase of cytosolic [Ca2+] and mitophagy by mitochondria stressors. High-fat diet (HFD) feeding augments pancreatic beta-cell mitophagy, probably as an adaptation to metabolic stress. HFD-induced increase of beta-cell mitophagy is reduced by tfeb KO, leading to increased ROS and decreased mitochondrial complex activity or oxygen consumption in tfeb-KO islets. In tfeb Delta beta-cell mice, HFD-induced glucose intolerance and beta-cell dysfunction are aggravated. Expression of mitophagy receptor genes including Optn or Calcoco2 is increased by mitochondrial or metabolic stressors in a TFEB-dependent manner, likely contributing to increased mitophagy. These results suggest that lysosomal Ca2+ release in conjunction with ER -> lysosome Ca2+ refilling is important for TFEB activation and mitophagy induction, which contributes to pancreatic beta-cell adaptation to metabolic stress. | - |
dc.format.extent | 3 | - |
dc.publisher | Taylor & Francis | - |
dc.title | Essential role of lysosomal Ca2+-mediated TFEB activation in mitophagy and functional adaptation of pancreatic β-cells to metabolic stress | - |
dc.type | Article | - |
dc.publisher.location | 미국 | - |
dc.identifier.doi | 10.1080/15548627.2022.2069956 | - |
dc.identifier.scopusid | 2-s2.0-85132674588 | - |
dc.identifier.wosid | 000789231100001 | - |
dc.identifier.bibliographicCitation | Autophagy, v.18, no.12, pp 3043 - 3045 | - |
dc.citation.title | Autophagy | - |
dc.citation.volume | 18 | - |
dc.citation.number | 12 | - |
dc.citation.startPage | 3043 | - |
dc.citation.endPage | 3045 | - |
dc.type.docType | Editorial Material | - |
dc.description.isOpenAccess | N | - |
dc.description.journalRegisteredClass | scie | - |
dc.description.journalRegisteredClass | scopus | - |
dc.relation.journalResearchArea | Cell Biology | - |
dc.relation.journalWebOfScienceCategory | Cell Biology | - |
dc.subject.keywordAuthor | Ca2+ | - |
dc.subject.keywordAuthor | lysosome | - |
dc.subject.keywordAuthor | mitophagy | - |
dc.subject.keywordAuthor | pancreatic beta-cells | - |
dc.subject.keywordAuthor | TFEB | - |
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