Enhancing Mitochondrial Function in Skeletal Muscle Cells through Metabolite Modulation: Therapeutic Implications for Muscle Metabolic Diseases

Our research investigates the role of cellular metabolites in mitochondrial bioenergetics within skeletal muscle cells, focusing on key intermediates that regulate ATP synthesis, oxidative phosphorylation, and overall energy efficiency. We examine how metabolites, including lactate, malate, succinate, and citrate, modulate mitochondrial respiration rates and influence ATP production under varying metabolic conditions. In our pre-clinical studies using skeletal muscle cell lines model, we demonstrate that lactate accumulation, common in hypoxic or highly glycolytic conditions, decreases mitochondrial efficiency by impairing oxygen utilization and ATP synthesis. In contrast, malate supplementation enhances mitochondrial oxygen consumption and ATP output, suggesting a protective role in counteracting metabolic stress. The results suggest that modulating intracellular metabolite concentrations can optimize mitochondrial function, providing potential therapeutic targets for muscle-related metabolic disorders, including type 2 diabetes and muscular dystrophy. This research contributes to understanding the dynamic relationship between cellular metabolites and mitochondrial bioenergetics, highlighting the potential for metabolic interventions to improve energy metabolism in skeletal muscle cells. USDA-ARS This abstract was presented at the American Physiology Summit 2025 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.