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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 | 이명식 | - |
dc.date.accessioned | 2023-06-02T00:53:08Z | - |
dc.date.available | 2023-06-02T00:53:08Z | - |
dc.date.issued | 2022-12 | - |
dc.identifier.issn | 1554-8627 | - |
dc.identifier.uri | https://ir.ymlib.yonsei.ac.kr/handle/22282913/194492 | - |
dc.description.abstract | Although the role of pancreatic β-cell macroautophagy/autophagy is well known, that of β-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 β-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 β-cell mitophagy, probably as an adaptation to metabolic stress. HFD-induced increase ofβ-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 Δβ-cell mice, HFD-induced glucose intolerance and β-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 β-cell adaptation to metabolic stress. | - |
dc.description.statementOfResponsibility | open | - |
dc.language | English | - |
dc.publisher | Taylor & Francis | - |
dc.relation.isPartOf | AUTOPHAGY | - |
dc.rights | CC BY-NC-ND 2.0 KR | - |
dc.subject.MESH | Animals | - |
dc.subject.MESH | Autophagy / physiology | - |
dc.subject.MESH | Basic Helix-Loop-Helix Leucine Zipper Transcription Factors / metabolism | - |
dc.subject.MESH | Calcium* / metabolism | - |
dc.subject.MESH | Lysosomes / metabolism | - |
dc.subject.MESH | Mice | - |
dc.subject.MESH | Mitophagy* / genetics | - |
dc.subject.MESH | Stress, Physiological | - |
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.contributor.college | College of Medicine (의과대학) | - |
dc.contributor.department | BioMedical Science Institute (의생명과학부) | - |
dc.contributor.googleauthor | Kihyoun Park | - |
dc.contributor.googleauthor | Myung-Shik Lee | - |
dc.identifier.doi | 10.1080/15548627.2022.2069956 | - |
dc.contributor.localId | A02752 | - |
dc.relation.journalcode | J00269 | - |
dc.identifier.eissn | 1554-8635 | - |
dc.identifier.pmid | 35468040 | - |
dc.subject.keyword | Ca2+ | - |
dc.subject.keyword | TFEB | - |
dc.subject.keyword | lysosome | - |
dc.subject.keyword | mitophagy | - |
dc.subject.keyword | pancreatic β-cells | - |
dc.contributor.alternativeName | Lee, Myung Shik | - |
dc.contributor.affiliatedAuthor | 이명식 | - |
dc.citation.volume | 18 | - |
dc.citation.number | 12 | - |
dc.citation.startPage | 3043 | - |
dc.citation.endPage | 3045 | - |
dc.identifier.bibliographicCitation | AUTOPHAGY, Vol.18(12) : 3043-3045, 2022-12 | - |
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