Abstract

Mitochondria are central to cellular energy metabolism, and their functional integrity is critical for muscle performance. This study investigates the effect of the compound MKT-077, a delocalized lipophilic cation, on the bioenergetic function of isolated mitochondria from mouse skeletal muscle. MKT-077 has been previously explored for its anti-cancer properties, but its impact on non-cancerous, highly metabolic tissues remains poorly understood. Using high-resolution respirometry, we assessed key parameters of mitochondrial function, including State 3 (ADP-stimulated) and State 4 (oligomycin-inhibited) respiration, respiratory control ratio (RCR), and the activity of specific respiratory chain complexes. Our findings demonstrate that MKT-077 significantly suppresses the functional activity of the isolated mitochondria, primarily by inhibiting Complex I and reducing the overall capacity for oxidative phosphorylation. This suppression suggests a potential mechanism for MKT-077's cellular toxicity and highlights a critical off-target effect on muscle bioenergetics, which is highly relevant to both cell biology and therapeutic development.