Abstract

Mitochondria are central to cellular energy metabolism, and their functional integrity is critical for muscle performance and overall cellular health. This study investigates the effect of the compound **MKT-077**, a delocalized lipophilic cation, on the bioenergetic function of **isolated mouse skeletal muscle mitochondria**. Given MKT-077's known accumulation in the mitochondrial matrix, the primary objective was to determine its impact on key respiratory parameters and membrane potential. Mitochondria were isolated from mouse skeletal muscle, and high-resolution respirometry was employed to measure oxygen consumption rates under various substrate conditions, including states 3 and 4 respiration. The results demonstrate that MKT-077 significantly **suppresses the functional activity** of these organelles, exhibiting a dose-dependent decrease in State 3 respiration and a reduction in the respiratory control ratio. Mechanistically, this suppression is likely due to MKT-077 interfering with the electron transport chain or disrupting the inner mitochondrial membrane's proton gradient. These findings highlight a potential off-target effect of MKT-0077, suggesting caution in its therapeutic application and providing a valuable model for studying mitochondrial dysfunction in skeletal muscle.