Mitochondrial-derived reactive oxygen species influence ADP sensitivity, but not CPT-I substrate sensitivity.

Autor: Barbeau PA; Human Health & Nutritional Sciences, University of Guelph, Guelph, Ontario, Canada., Miotto PM; Human Health & Nutritional Sciences, University of Guelph, Guelph, Ontario, Canada., Holloway GP; Human Health & Nutritional Sciences, University of Guelph, Guelph, Ontario, Canada ghollowa@uoguelph.ca.
Jazyk: angličtina
Zdroj: The Biochemical journal [Biochem J] 2018 Sep 28; Vol. 475 (18), pp. 2997-3008. Date of Electronic Publication: 2018 Sep 28.
DOI: 10.1042/BCJ20180419
Abstrakt: The mechanisms regulating oxidative phosphorylation during exercise remain poorly defined; however, key mitochondrial proteins, including carnitine palmitoyltransferase-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 (wild type) and transgenic mice (MCAT, mitochondrial-targeted catalase transgenic) 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 that mitochondrial ROS does not regulate CPT-I. In contrast, while mitochondrial protein content, maximal coupled respiration, and ADP (adenosine diphosphate) sensitivity in resting muscle were unchanged in the absence of mitochondrial ROS, exercise increased the apparent ADP K m (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 K m was increased only in the presence of mitochondrial ROS. This basic pattern was also mirrored in the ability of ADP to suppress mitochondrial H 2 O 2 emission rates, as exercise decreased the suppression of H 2 O 2 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 signaling as a regulator of oxidative phosphorylation.
(© 2018 The Author(s). Published by Portland Press Limited on behalf of the Biochemical Society.)
Databáze: MEDLINE
Externí odkaz: