Mitochondrial GCN5L1 coordinates with YME1L and MICOS to remodel mitochondrial cristae in white adipocytes and modulate obesity
Summary: The relationship between mitochondrial architecture and energy homeostasis in adipose tissues is not well understood. In this study, we utilized GCN5L1-knockout mice in white (AKO) and brown (BKO) adipose tissues to examine mitochondrial homeostasis in adipose tissues. GCN5L1, a regulator o...
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Elsevier
2025-05-01
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| Series: | Cell Reports |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S221112472500453X |
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| author | Juan Xu Qiqi Zhang Xinyu Yang Qiqi Tang Yitong Han Jiahui Meng Jiaqi Zhang Xin Lu Danni Wang Jing Liu Bo Shan Xue Bai Kai Zhang Longhao Sun Lingdi Wang Lu Zhu |
| author_facet | Juan Xu Qiqi Zhang Xinyu Yang Qiqi Tang Yitong Han Jiahui Meng Jiaqi Zhang Xin Lu Danni Wang Jing Liu Bo Shan Xue Bai Kai Zhang Longhao Sun Lingdi Wang Lu Zhu |
| author_sort | Juan Xu |
| collection | DOAJ |
| description | Summary: The relationship between mitochondrial architecture and energy homeostasis in adipose tissues is not well understood. In this study, we utilized GCN5L1-knockout mice in white (AKO) and brown (BKO) adipose tissues to examine mitochondrial homeostasis in adipose tissues. GCN5L1, a regulator of mitochondrial metabolism and dynamics, influences resistance to high-fat-diet-induced obesity in AKO but not BKO mice. This resistance is mediated by an increase in mitochondrial cristae that stabilizes oxidative phosphorylation (OXPHOS) complexes and enhances energy expenditure. Our protein-interactome analysis reveals that GCN5L1 is associated with the mitochondrial crista complex MICOS (MIC13) and the protease YME1L, facilitating the degradation of MICOS and disassembly of cristae during obesity. This interaction results in decreased OXPHOS levels and subsequent adipocyte expansion. Accumulation of GCN5L1 in the mitochondrial intermembrane space is triggered by a high-fat diet. Our findings highlight a regulatory pathway involving YME1L/GCN5L1/MIC13 that remodels mitochondrial cristae in WAT in response to overnutrition-induced obesity. |
| format | Article |
| id | doaj-art-198bfad3acf9478d93e04b78df171ca0 |
| institution | OA Journals |
| issn | 2211-1247 |
| language | English |
| publishDate | 2025-05-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Cell Reports |
| spelling | doaj-art-198bfad3acf9478d93e04b78df171ca02025-08-20T02:28:19ZengElsevierCell Reports2211-12472025-05-0144511568210.1016/j.celrep.2025.115682Mitochondrial GCN5L1 coordinates with YME1L and MICOS to remodel mitochondrial cristae in white adipocytes and modulate obesityJuan Xu0Qiqi Zhang1Xinyu Yang2Qiqi Tang3Yitong Han4Jiahui Meng5Jiaqi Zhang6Xin Lu7Danni Wang8Jing Liu9Bo Shan10Xue Bai11Kai Zhang12Longhao Sun13Lingdi Wang14Lu Zhu15Department of Pharmacology, State Key Laboratory of Experimental Hematology, Tianjin Key Laboratory of Inflammatory Biology, The Province and Ministry Co-sponsored Collaborative Innovation Center for Medical Epigenetics, NHC Key Laboratory of Hormones and Development, Chu Hsien-I Memorial Hospital and Tianjin Institute of Endocrinology, School of Basic Medical Sciences, Tianjin Medical University, Tianjin, ChinaDepartment of Pharmacology, State Key Laboratory of Experimental Hematology, Tianjin Key Laboratory of Inflammatory Biology, The Province and Ministry Co-sponsored Collaborative Innovation Center for Medical Epigenetics, NHC Key Laboratory of Hormones and Development, Chu Hsien-I Memorial Hospital and Tianjin Institute of Endocrinology, School of Basic Medical Sciences, Tianjin Medical University, Tianjin, ChinaDepartment of Pharmacology, State Key Laboratory of Experimental Hematology, Tianjin Key Laboratory of Inflammatory Biology, The Province and Ministry Co-sponsored Collaborative Innovation Center for Medical Epigenetics, NHC Key Laboratory of Hormones and Development, Chu Hsien-I Memorial Hospital and Tianjin Institute of Endocrinology, School of Basic Medical Sciences, Tianjin Medical University, Tianjin, ChinaDepartment of Physiology and Pathophysiology, Tianjin Key Laboratory of Cell Homeostasis and Major Diseases, School of Basic Medical Sciences, Tianjin Medical University, Tianjin, ChinaDepartment of General Surgery, Tianjin Medical University General Hospital, Tianjin, ChinaDepartment of Pharmacology, State Key Laboratory of Experimental Hematology, Tianjin Key Laboratory of Inflammatory Biology, The Province and Ministry Co-sponsored Collaborative Innovation Center for Medical Epigenetics, NHC Key Laboratory of Hormones and Development, Chu Hsien-I Memorial Hospital and Tianjin Institute of Endocrinology, School of Basic Medical Sciences, Tianjin Medical University, Tianjin, ChinaDepartment of Physiology and Pathophysiology, Tianjin Key Laboratory of Cell Homeostasis and Major Diseases, School of Basic Medical Sciences, Tianjin Medical University, Tianjin, ChinaDepartment of Physiology and Pathophysiology, Tianjin Key Laboratory of Cell Homeostasis and Major Diseases, School of Basic Medical Sciences, Tianjin Medical University, Tianjin, ChinaDepartment of Pharmacology, State Key Laboratory of Experimental Hematology, Tianjin Key Laboratory of Inflammatory Biology, The Province and Ministry Co-sponsored Collaborative Innovation Center for Medical Epigenetics, NHC Key Laboratory of Hormones and Development, Chu Hsien-I Memorial Hospital and Tianjin Institute of Endocrinology, School of Basic Medical Sciences, Tianjin Medical University, Tianjin, ChinaState Key Laboratory of Experimental Hematology, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin 300020, ChinaZhejiang Key Laboratory of Pancreatic Disease, The First Affiliated Hospital, Institute of Translational Medicine, Zhejiang Key Laboratory of Frontier Medical Research on Cancer Metabolism, Zhejiang University School of Medicine, Zhejiang University, Hangzhou, Zhejiang, ChinaDepartment of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Tianjin Medical University, Tianjin, ChinaDepartment of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Tianjin Medical University, Tianjin, ChinaDepartment of General Surgery, Tianjin Medical University General Hospital, Tianjin, China; Corresponding authorDepartment of Physiology and Pathophysiology, Tianjin Key Laboratory of Cell Homeostasis and Major Diseases, School of Basic Medical Sciences, Tianjin Medical University, Tianjin, China; Corresponding authorDepartment of Pharmacology, State Key Laboratory of Experimental Hematology, Tianjin Key Laboratory of Inflammatory Biology, The Province and Ministry Co-sponsored Collaborative Innovation Center for Medical Epigenetics, NHC Key Laboratory of Hormones and Development, Chu Hsien-I Memorial Hospital and Tianjin Institute of Endocrinology, School of Basic Medical Sciences, Tianjin Medical University, Tianjin, China; Department of Gynecology and Obstetrics, Tianjin Medical University General Hospital, Tianjin, China; Corresponding authorSummary: The relationship between mitochondrial architecture and energy homeostasis in adipose tissues is not well understood. In this study, we utilized GCN5L1-knockout mice in white (AKO) and brown (BKO) adipose tissues to examine mitochondrial homeostasis in adipose tissues. GCN5L1, a regulator of mitochondrial metabolism and dynamics, influences resistance to high-fat-diet-induced obesity in AKO but not BKO mice. This resistance is mediated by an increase in mitochondrial cristae that stabilizes oxidative phosphorylation (OXPHOS) complexes and enhances energy expenditure. Our protein-interactome analysis reveals that GCN5L1 is associated with the mitochondrial crista complex MICOS (MIC13) and the protease YME1L, facilitating the degradation of MICOS and disassembly of cristae during obesity. This interaction results in decreased OXPHOS levels and subsequent adipocyte expansion. Accumulation of GCN5L1 in the mitochondrial intermembrane space is triggered by a high-fat diet. Our findings highlight a regulatory pathway involving YME1L/GCN5L1/MIC13 that remodels mitochondrial cristae in WAT in response to overnutrition-induced obesity.http://www.sciencedirect.com/science/article/pii/S221112472500453XCP: MetabolismCP: Cell biology |
| spellingShingle | Juan Xu Qiqi Zhang Xinyu Yang Qiqi Tang Yitong Han Jiahui Meng Jiaqi Zhang Xin Lu Danni Wang Jing Liu Bo Shan Xue Bai Kai Zhang Longhao Sun Lingdi Wang Lu Zhu Mitochondrial GCN5L1 coordinates with YME1L and MICOS to remodel mitochondrial cristae in white adipocytes and modulate obesity Cell Reports CP: Metabolism CP: Cell biology |
| title | Mitochondrial GCN5L1 coordinates with YME1L and MICOS to remodel mitochondrial cristae in white adipocytes and modulate obesity |
| title_full | Mitochondrial GCN5L1 coordinates with YME1L and MICOS to remodel mitochondrial cristae in white adipocytes and modulate obesity |
| title_fullStr | Mitochondrial GCN5L1 coordinates with YME1L and MICOS to remodel mitochondrial cristae in white adipocytes and modulate obesity |
| title_full_unstemmed | Mitochondrial GCN5L1 coordinates with YME1L and MICOS to remodel mitochondrial cristae in white adipocytes and modulate obesity |
| title_short | Mitochondrial GCN5L1 coordinates with YME1L and MICOS to remodel mitochondrial cristae in white adipocytes and modulate obesity |
| title_sort | mitochondrial gcn5l1 coordinates with yme1l and micos to remodel mitochondrial cristae in white adipocytes and modulate obesity |
| topic | CP: Metabolism CP: Cell biology |
| url | http://www.sciencedirect.com/science/article/pii/S221112472500453X |
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