Stanford University, Stanford, CA, USA; Insitro, San Francisco, CA, USA.
Stanford University, Stanford, CA, USA.
Cell Metab. 2024 Jun 4;36(6):1411-1429.e10. doi: 10.1016/j.cmet.2023.12.021. Epub 2024 May 2.
Mitochondria have diverse functions critical to whole-body metabolic homeostasis. Endurance training alters mitochondrial activity, but systematic characterization of these adaptations is lacking. Here, the Molecular Transducers of Physical Activity Consortium mapped the temporal, multi-omic changes in mitochondrial analytes across 19 tissues in male and female rats trained for 1, 2, 4, or 8 weeks. Training elicited substantial changes in the adrenal gland, brown adipose, colon, heart, and skeletal muscle. The colon showed non-linear response dynamics, whereas mitochondrial pathways were downregulated in brown adipose and adrenal tissues. Protein acetylation increased in the liver, with a shift in lipid metabolism, whereas oxidative proteins increased in striated muscles. Exercise-upregulated networks were downregulated in human diabetes and cirrhosis. Knockdown of the central network protein 17-beta-hydroxysteroid dehydrogenase 10 (HSD17B10) elevated oxygen consumption, indicative of metabolic stress. We provide a multi-omic, multi-tissue, temporal atlas of the mitochondrial response to exercise training and identify candidates linked to mitochondrial dysfunction.
线粒体具有多种功能，对全身代谢稳态至关重要。耐力训练会改变线粒体的活性，但系统地描述这些适应性变化的研究还很缺乏。在这里，运动分子转导联盟（Molecular Transducers of Physical Activity Consortium）绘制了雄性和雌性大鼠经过 1、2、4 或 8 周训练后，19 种组织中线粒体分析物的时间和多组学变化图谱。训练引起了肾上腺、棕色脂肪、结肠、心脏和骨骼肌的显著变化。结肠表现出非线性的反应动力学，而棕色脂肪和肾上腺组织中的线粒体途径被下调。肝脏中的蛋白质乙酰化增加，伴随着脂质代谢的转变，而横纹肌中的氧化蛋白增加。在人类糖尿病和肝硬化中，运动上调的网络被下调。中央网络蛋白 17-β-羟类固醇脱氢酶 10（HSD17B10）的敲低会增加耗氧量，表明存在代谢应激。我们提供了一个多组学、多组织、时间性的线粒体对运动训练反应图谱，并确定了与线粒体功能障碍相关的候选物。
