Barbeau 2018 Biochem J
|Barbeau PA, Miotto PM, Holloway GP (2018) Mitochondrial derived reactive oxygen species influence ADP sensitivity, but not CPT-I substrate sensitivity. Biochem J 475:2997-3008.|
Abstract: The mechanisms regulating oxidative phosphorylation during exercise remain poorly defined, however key mitochondrial proteins, including carnitine-palmitoyl transferase-I (CPT-I) and adenine-nucleotide translocase have redox sensitive sites. Interestingly muscle contraction has recently been shown to increase mitochondrial membrane potential and reactive oxygen species (ROS) production, therefore we aimed to determine if mitochondrial derived ROS influences bioenergetic responses to exercise. Specifically, we examined the influence of acute exercise on mitochondrial bioenergetics in WT and transgenic mice (MCAT) possessing attenuated mitochondrial ROS. We found that ablating mitochondrial ROS did not alter palmitoyl-CoA (P-CoA) respiratory kinetics or influence the exercise-mediated reductions in malonyl-CoA sensitivity, suggesting mitochondrial ROS does not regulate CPT-I. In contrast, while mitochondrial protein content, maximal coupled respiration, and ADP sensitivity in resting muscle were unchanged in the absence of mitochondrial ROS, exercise increased the apparent ADP Km (decreased ADP sensitivity) ~30% only in WT mice. Moreover, while the presence of P-CoA decreased ADP sensitivity, it did not influence the basic response to exercise, as the apparent ADP Km was increased only in the presence of mitochondrial ROS. This basic pattern was also mirrored in the ability of ADP to supress mitochondrial H2O2 emission rates, as exercise decreased the suppression of H2O2 only in WT mice. Altogether, these data demonstrate that while exercise-induced mitochondrial derived ROS does not influence CPT-I substrate sensitivity, it inhibits ADP sensitivity independent of P-CoA. These data implicate mitochondrial redox signalling as a regulator of oxidative phosphorylation.
Labels: MiParea: Respiration, Exercise physiology;nutrition;life style
Organism: Mouse Tissue;cell: Skeletal muscle Preparation: Permeabilized tissue
Coupling state: OXPHOS Pathway: F, N, NS HRR: Oxygraph-2k