Pancreatic β-cell mitophagy as an adaptive response to metabolic stress and the underlying mechanism that involves lysosomal Ca<SUP>2+</SUP> release
DC Field | Value | Language |
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dc.contributor.author | Oh, Soo-Jin | - |
dc.contributor.author | Park, Kihyoun | - |
dc.contributor.author | Sonn, Seong Keun | - |
dc.contributor.author | Oh, Goo Taeg | - |
dc.contributor.author | Lee, Myung-Shik | - |
dc.date.accessioned | 2023-12-14T06:31:32Z | - |
dc.date.available | 2023-12-14T06:31:32Z | - |
dc.date.issued | 2023-09 | - |
dc.identifier.issn | 1226-3613 | - |
dc.identifier.issn | 2092-6413 | - |
dc.identifier.uri | https://scholarworks.bwise.kr/sch/handle/2021.sw.sch/25525 | - |
dc.description.abstract | Mitophagy is an excellent example of selective autophagy that eliminates damaged or dysfunctional mitochondria, and it is crucial for the maintenance of mitochondrial integrity and function. The critical roles of autophagy in pancreatic ss-cell structure and function have been clearly shown. Furthermore, morphological abnormalities and decreased function of mitochondria have been observed in autophagy-deficient ss-cells, suggesting the importance of ss-cell mitophagy. However, the role of authentic mitophagy in ss-cell function has not been clearly demonstrated, as mice with pancreatic ss-cell-specific disruption of Parkin, one of the most important players in mitophagy, did not exhibit apparent abnormalities in ss-cell function or glucose homeostasis. Instead, the role of mitophagy in pancreatic ss-cells has been investigated using ss-cell-specific Tfeb-knockout mice (Tfeb(Delta ss-cell) mice); Tfeb is a master regulator of lysosomal biogenesis or autophagy gene expression and participates in mitophagy. Tfeb(Delta ss-cell) mice were unable to adaptively increase mitophagy or mitochondrial complex activity in response to high-fat diet (HFD)-induced metabolic stress. Consequently, Tfeb(Delta ss-cell) mice exhibited impaired ss-cell responses and further exacerbated metabolic deterioration after HFD feeding. TFEB was activated by mitochondrial or metabolic stress-induced lysosomal Ca2+ release, which led to calcineurin activation and mitophagy. After lysosomal Ca2+ release, depleted lysosomal Ca2+ stores were replenished by ER Ca2+ through ER -> lysosomal Ca2+ refilling, which supplemented the low lysosomal Ca2+ capacity. The importance of mitophagy in ss-cell function was also demonstrated in mice that developed ss-cell dysfunction and glucose intolerance after treatment with a calcineurin inhibitor that hampered TFEB activation and mitophagy. | - |
dc.language | 영어 | - |
dc.language.iso | ENG | - |
dc.publisher | SPRINGERNATURE | - |
dc.title | Pancreatic β-cell mitophagy as an adaptive response to metabolic stress and the underlying mechanism that involves lysosomal Ca<SUP>2+</SUP> release | - |
dc.type | Article | - |
dc.publisher.location | 영국 | - |
dc.identifier.doi | 10.1038/s12276-023-01055-4 | - |
dc.identifier.scopusid | 2-s2.0-85169162126 | - |
dc.identifier.wosid | 001065142700004 | - |
dc.identifier.bibliographicCitation | EXPERIMENTAL AND MOLECULAR MEDICINE | - |
dc.citation.title | EXPERIMENTAL AND MOLECULAR MEDICINE | - |
dc.type.docType | Review; Early Access | - |
dc.identifier.kciid | ART003003961 | - |
dc.description.isOpenAccess | Y | - |
dc.description.journalRegisteredClass | scie | - |
dc.description.journalRegisteredClass | scopus | - |
dc.description.journalRegisteredClass | kci | - |
dc.relation.journalResearchArea | Biochemistry & Molecular Biology | - |
dc.relation.journalResearchArea | Research & Experimental Medicine | - |
dc.relation.journalWebOfScienceCategory | Biochemistry & Molecular Biology | - |
dc.relation.journalWebOfScienceCategory | Medicine, Research & Experimental | - |
dc.subject.keywordPlus | INSULIN-RESISTANCE | - |
dc.subject.keywordPlus | MITOCHONDRIAL | - |
dc.subject.keywordPlus | AUTOPHAGY | - |
dc.subject.keywordPlus | PARKIN | - |
dc.subject.keywordPlus | PINK1 | - |
dc.subject.keywordPlus | CALCINEURIN | - |
dc.subject.keywordPlus | UBIQUITIN | - |
dc.subject.keywordPlus | PALMITATE | - |
dc.subject.keywordPlus | CLEC16A | - |
dc.subject.keywordPlus | MODEL | - |
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