小柯机器人

美国丹娜-法伯癌症研究所Pere Puigserver团队近期取得重要工作进展。他们研究发现，肝线粒体嵴组织蛋白MIC19通过改变核苷酸代谢促进能量消耗和行人运动。相关研究成果2023年7月19日在线发表于《细胞—代谢》杂志上。

据介绍，肝脏线粒体在进食和禁食时进行结构重塑，维持能量稳态。然而，驱动这些变化的具体成分和分子机制及其对能量代谢的影响仍不清楚。

通过比较小鼠蛋白质组学，研究人员发现，禁食通过上调MICOS复合物的一个亚基MIC19，诱导肝脏中菌株特异性线粒体嵴的形成。在肝脏中强制表达MIC19可促进嵴的形成、线粒体呼吸和脂肪酸氧化，同时抑制糖异生。过表达肝脏MIC19的小鼠表现出对饮食诱导的肥胖的抵抗和改善的葡萄糖稳态。MIC19过表达小鼠表现出能量消耗增加和步行运动增加。代谢产物分析显示，尿嘧啶在这些小鼠的肝脏中积聚是由于尿苷磷酸化酶UPP2活性增加。

此外，补充尿嘧啶的饮食增加了野生型小鼠的运动能力。

因此，MIC19诱导的肝脏线粒体嵴的形成增加了尿嘧啶作为促进运动的信号，并且对饮食诱导的肥胖具有保护作用。

附：英文原文

Title: Liver mitochondrial cristae organizing protein MIC19 promotes energy expenditure and pedestrian locomotion by altering nucleotide metabolism

Author: Jee Hyung Sohn, Beste Mutlu, Pedro Latorre-Muro, Jiaxin Liang, Christopher F. Bennett, Kfir Sharabi, Noa Kantorovich, Mark Jedrychowski, Steven P. Gygi, Alexander S. Banks, Pere Puigserver

Issue&Volume: 2023-07-19

Abstract: Liver mitochondria undergo architectural remodeling that maintains energy homeostasisin response to feeding and fasting. However, the specific components and molecularmechanisms driving these changes and their impact on energy metabolism remain unclear.Through comparative mouse proteomics, we found that fasting induces strain-specificmitochondrial cristae formation in the liver by upregulating MIC19, a subunit of theMICOS 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 improvedglucose homeostasis. Interestingly, MIC19 overexpressing mice exhibit elevated energyexpenditure and increased pedestrian locomotion. Metabolite profiling revealed thaturacil accumulates in the livers of these mice due to increased uridine phosphorylaseUPP2 activity. Furthermore, uracil-supplemented diet increases locomotion in wild-typemice. Thus, MIC19-induced mitochondrial cristae formation in the liver increases uracilas a signal to promote locomotion, with protective effects against diet-induced obesity.

DOI: 10.1016/j.cmet.2023.06.015

Source: https://www.cell.com/cell-metabolism/fulltext/S1550-4131(23)00225-5

Cell Metabolism：《细胞—代谢》，创刊于2005年。隶属于细胞出版社，最新IF：31.373
官方网址：https://www.cell.com/cell-metabolism/home
投稿链接：https://www.editorialmanager.com/cell-metabolism/default.aspx