한빛사논문
- 조회644
Jee Hyung Sohn,1,2,4 Beste Mutlu,1,2,4 Pedro Latorre-Muro,1,2,4 Jiaxin Liang,1,2 Christopher F. Bennett,1,2 Kfir Sharabi,1,2 Noa Kantorovich,1,2 Mark Jedrychowski,2 Steven P. Gygi,2 Alexander S. Banks,3 and Pere Puigserver1,2,5,*
1Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, MA 02215, USA
2Department of Cell Biology, Blavatnik Institute, Harvard Medical School, Boston, MA 02215, USA
3Division of Endocrinology, Diabetes and Metabolism, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA, USA
4These authors contributed equally
5Lead contact
*Corresponding author: correspondence to Pere Puigserver
Abstract
Liver mitochondria undergo architectural remodeling that maintains energy homeostasis in response to feeding and fasting. However, the specific components and molecular mechanisms driving these changes and their impact on energy metabolism remain unclear. Through comparative mouse proteomics, we found that fasting induces strain-specific mitochondrial cristae formation in the liver by upregulating MIC19, a subunit of the MICOS complex. Enforced MIC19 expression in the liver promotes cristae formation, mitochondrial respiration, and fatty acid oxidation while suppressing gluconeogenesis. Mice overexpressing hepatic MIC19 show resistance to diet-induced obesity and improved glucose homeostasis. Interestingly, MIC19 overexpressing mice exhibit elevated energy expenditure and increased pedestrian locomotion. Metabolite profiling revealed that uracil accumulates in the livers of these mice due to increased uridine phosphorylase UPP2 activity. Furthermore, uracil-supplemented diet increases locomotion in wild-type mice. Thus, MIC19-induced mitochondrial cristae formation in the liver increases uracil as a signal to promote locomotion, with protective effects against diet-induced obesity.
논문정보
- Research article
- 2023년 07월 (BRIC 등록일 2023-07-21)
- 국외 연구진
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