Mitochondrial GCN5L1 coordinates with YME1L and MICOS to remodel mitochondrial cristae in white adipocytes and modulate obesity.

IF 7.5 1区生物学 Q1 CELL BIOLOGY

Cell reports Pub Date : 2025-05-07 DOI:10.1016/j.celrep.2025.115682

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

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引用次数: 0

Abstract

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.

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线粒体GCN5L1与YME1L和MICOS协同重组白色脂肪细胞线粒体嵴，调节肥胖。

线粒体结构与脂肪组织能量稳态之间的关系尚不清楚。在这项研究中，我们利用白色（AKO）和棕色（BKO）脂肪组织中的gcn5l1基因敲除小鼠来检测脂肪组织中的线粒体稳态。GCN5L1是线粒体代谢和动力学的调节因子，影响AKO小鼠对高脂肪饮食诱导的肥胖的抵抗，但不影响BKO小鼠。这种抗性是由线粒体嵴的增加介导的，线粒体嵴稳定氧化磷酸化（OXPHOS）复合物并增加能量消耗。我们的蛋白质相互作用组分析显示，GCN5L1与线粒体嵴复合物MICOS （MIC13）和蛋白酶YME1L相关，促进肥胖期间MICOS的降解和嵴的拆卸。这种相互作用导致OXPHOS水平下降和随后的脂肪细胞扩张。GCN5L1在线粒体膜间隙的积累是由高脂肪饮食引发的。我们的研究结果强调了一个涉及YME1L/GCN5L1/MIC13的调控途径，该途径在WAT中重塑线粒体嵴，以应对营养过剩引起的肥胖。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Cell reports CELL BIOLOGY-

CiteScore

13.80

自引率

1.10%

发文量

1305

审稿时长

77 days

期刊介绍： Cell Reports publishes high-quality research across the life sciences and focuses on new biological insight as its primary criterion for publication. The journal offers three primary article types: Reports, which are shorter single-point articles, research articles, which are longer and provide deeper mechanistic insights, and resources, which highlight significant technical advances or major informational datasets that contribute to biological advances. Reviews covering recent literature in emerging and active fields are also accepted. The Cell Reports Portfolio includes gold open-access journals that cover life, medical, and physical sciences, and its mission is to make cutting-edge research and methodologies available to a wide readership. The journal's professional in-house editors work closely with authors, reviewers, and the scientific advisory board, which consists of current and future leaders in their respective fields. The advisory board guides the scope, content, and quality of the journal, but editorial decisions are independently made by the in-house scientific editors of Cell Reports.