Work

Chamber oxygen concentration impacts mitochondrial function and hydrogen peroxide appearance in permeabilized human skeletal muscle fibers

Year: 2025

Type: article

Abstract: Skeletal muscle mitochondrial respiration is commonly assessed ex vivo using permeabilized fibers in media with high oxygen (O 2 ) concentrations to ensure that O 2 availability does not limit respiration. However, high O 2 concentrations also increase the production of reactive O 2 species that can negatively affect respiration. In this study, we tested the hypotheses that permeabilized fiber mitochondria in a high, compared to low, O 2 concentration would (i) not be different at maximal state 3 respiration rate (V max ), (ii) have lower submaximal respiration rates at submaximal O 2 concentrations, and (iii) have greater total cumulative hydrogen peroxide (H 2 O 2 ) appearance. We continuously monitored mitochondrial state 3 respiration and H 2 O 2 appearance rates using high-resolution respirometry in permeabilized skeletal muscle fibers (12 untrained participants; 22 ± 4 yrs) with either control (~127 mmHg; CON) or high (~327 mmHg; HIGH) partial pressures of O 2 (PO 2 ). V max was not different between conditions (HIGH: 80.7 ± 16.7 vs. CON: 82.3 ± 18.7 pmol/s/mg, p = 0.695). The PO 2 at 80 % V max (P 80 ) was greater in HIGH (73.9 ± 25.5 vs. 28.0 ± 7.1 mmHg, p < 0.001) and respiration rates at 5–60 mmHg PO 2 were lower for HIGH than CON (all p < 0.001). Additionally, the total cumulative H 2 O 2 appearance was greater in HIGH than CON ( n = 11; 51.5 ± 23.2 vs. 18.3 ± 10.3 pmol/mg, p < 0.001), and this difference was directly correlated with the difference in P 80 ( r = 0.655, p = 0.029). The current findings support that a high O 2 concentration, by itself, does not appear to affect V max in the permeabilized skeletal muscle fiber preparation, but the corollary increase in H 2 O 2 exposure may diminish mitochondrial state 3 respiratory function.

Source: Biochimica et Biophysica Acta (BBA) - Bioenergetics

DOI: 10.1016/j.bbabio.2025.149568