Vinokurov Andrey Y, Bazhenov Pavel A, Pogonyalova Marina Y, Seryogina Evgenia S, Vetrova Ekaterina A, Andreeva Larisa, Abramov Andrey Y, Angelova Plamena R
Cell Physiology and Pathology Laboratory, Orel State University, Orel, Russia.
Mitocholine Ltd., London, UK.
J Cell Mol Med. 2025 May;29(9):e70588. doi: 10.1111/jcmm.70588.
Skeletal muscles constantly consume energy, and this consumption level increases correspondingly to the levels of physical activity. Mitochondrial energy metabolism requires constant supplementation with oxygen and substrates for ATP production. Limitation of the mitochondrial substrate supply leads to energy deprivation, which may be followed by sarcopenia and weight loss. Activation of mitochondrial energy metabolism can also stimulate the production of reactive oxygen species and oxidative stress. Here, we studied the effect of various mitochondrial substrates on the energy metabolism of primary skeletal myotubes and how it affects redox balance. We found that as individual components-glutamate, succinate, nicotinamide (NAM) as well as in combination-dicholine succinate (DISU) plus NAM, they increase mitochondrial membrane potential, alter NADH and FAD redox indices, which leads to an increased energy capacity of the skeletal myotubes. Changes in mitochondrial metabolism increased ROS production in mitochondria and cytosol but induced only a minor decrease in the level of the endogenous antioxidant reduced glutathione. Supplementation of young and aged rats with DISU + NAM through the drinking water for 7 days significantly increased myotube diameter in both age groups. Thus, provision of the myotubes with mitochondrial metabolism substrates activates energy metabolism and increases energy capacity but has no effect on oxidative stress. Moreover, it increases myotubes' diameters in young and aged rodent sarcopenia models in vivo.
骨骼肌持续消耗能量，且这种消耗水平会随着身体活动水平相应增加。线粒体能量代谢需要持续补充氧气和底物以生成三磷酸腺苷（ATP）。线粒体底物供应受限会导致能量剥夺，进而可能引发肌肉减少症和体重减轻。线粒体能量代谢的激活也会刺激活性氧的产生和氧化应激。在此，我们研究了各种线粒体底物对原代骨骼肌肌管能量代谢的影响以及它如何影响氧化还原平衡。我们发现，作为单独成分的谷氨酸、琥珀酸、烟酰胺（NAM），以及组合形式的琥珀酸二胆碱（DISU）加NAM，它们都会增加线粒体膜电位，改变烟酰胺腺嘌呤二核苷酸（NADH）和黄素腺嘌呤二核苷酸（FAD）的氧化还原指数，这会导致骨骼肌肌管的能量容量增加。线粒体代谢的变化增加了线粒体和细胞质中的活性氧生成，但仅使内源性抗氧化剂还原型谷胱甘肽水平略有下降。通过饮用水给年轻和老年大鼠补充DISU + NAM 7天，两个年龄组的肌管直径均显著增加。因此，为肌管提供线粒体代谢底物可激活能量代谢并增加能量容量，但对氧化应激没有影响。此外，它还能增加年轻和老年啮齿动物肌肉减少症模型体内的肌管直径。
