Palmitoyl-CoA Inhibition of Mitochondrial ADP Sensitivity is Attenuated by Exercise Training in Human Skeletal Muscle

A hallmark of improved metabolic control is a reduced free ADP requirement for a given workload (increased ADP sensitivity). In contrast to in vivo data, in situ assessments suggest that mitochondrial ADP sensitivity is decreased following exercise training, implying external regulation that is not recapitulated in situ. One previously unexplored regulator is palmitoyl-CoA (P-CoA), a lipid metabolism intermediate that inhibits the mitochondrial ADP transport protein adenine nucleotide transferase (ANT). This thesis: 1) established reduced mitochondrial ADP sensitivity following exercise training in middle aged males using permeabilized muscle fibre bundles (PmFB), 2) determined a methodology to evaluate ADP kinetics in PmFB in the presence of P-CoA, and 3) found increased mitochondrial ADP sensitivity in the presence of P-CoA following training. These data suggest that P-CoA is a key regulator of oxidative phosphorylation and direct future exploration of mitochondrial function towards the control of ADP transport via ANT and the effects of exercise on the P-CoA-ANT interaction