Biological sex does not impact intrinsic mitochondrial respiration supported by complexes I and II in human skeletal muscle

The effect of biological sex on rates of skeletal muscle mitochondrial respiration supported by creatine-dependent phosphate shuttling was previously unknown. The aim of this investigation was to test the hypothesis that females and males matched for peak oxygen uptake normalized to fat-free mass would not exhibit differences in rates of mass-specific and intrinsic mitochondrial respiration in the presence or absence of creatine. Rates of mass-specific and intrinsic complex I (pyruvate and malate)- and complex I+II-supported, adenosine diphosphate (ADP)-stimulated mitochondrial respiration in the presence and absence of 20 mM creatine were measured via high-resolution respirometry. Total, intermyofibrillar and subsarcolemmal mitochondrial volume density were analysed using transmission electron microscopy. Rates of intrinsic mitochondrial respiration were obtained by normalizing mass-specific respiration rates to total mitochondrial volume density and total electron transport chain subunit protein content. Overall, there was no effect of sex on rates of mass-specific or intrinsic mitochondrial respiration in the presence or absence of creatine. There was also no effect of sex on total, intermyofibrillar and subsarcolemmal mitochondrial volume density or electron transport chain subunit protein content. Our data demonstrate an overall lack of sex-based differences in rates of intrinsic complex I- and complex I+II-supported, ADP-stimulated mitochondrial respiration in the presence or absence of creatine in females and males matched for aerobic fitness. Thus, biological sex per se does not appear to modulate intrinsic skeletal muscle mitochondrial respiration in healthy young adults.