Sex differences in mitochondrial bioenergetics and antioxidant buffering capacity in PBMCs from healthy young men and women

Reduced oxidative stress is a potential mechanism contributing to lower cardiovascular risk in premenopausal women compared to age-matched men. The mitochondria are an important source of reactive oxygen species (mtROS), but an imbalance between mtROS production and antioxidant (AOX) capacity results in oxidative stress, which may have deleterious impacts on cardiovascular health. This study examined potential sex differences in mitochondrial bioenergetics and AOX buffering capacity in peripheral blood mononuclear cells (PBMCs) isolated from the whole blood of healthy, young men (n = 4; 20 ± 1 yrs) and women (n = 6; 22 ± 3 yrs). Immediately after PBMC isolation, high-resolution respirometry was used with a bioenergetic creatine kinase (CK) clamp to simultaneously measure mitochondrial respiration rate (JO 2 ) and membrane potential (mtMP) at clamped physiological ATP: ADP ratios. MtROS emission was measured as real-time H 2 O 2 emission, and inhibitors of glutathione reductase and thioredoxin/peroxiredoxin allowed the quantification of H 2 O 2 production. AOX buffering capacity was calculated as the percentage of H 2 O 2 produced but not emitted. There were no sex differences in JO 2 (p ≥ 0.24) or electron conductance (p = 0.25) throughout the CK clamp. Likewise, there were no sex differences in mtMP (p ≥ 0.07). Although there were no statistical differences in H 2 O 2 emission (Men, 0.83 ± 0.22 pmol/min/million cells; Women, 0.64 ± 0.27 pmol/min/million cells; p = 0.46) or production (Men, 1.96 ± 0.26 pmol/min/million cells; Women, 2.19 ± 0.57 pmol/min/million cells; p = 0.37), AOX buffering capacity was greater in women compared to men (Men, 57.56 ± 11.79%; Women, 71.47 ± 8.29%; p = 0.03). Despite no sex differences in mitochondrial bioenergetics, these data suggest that PBMC AOX buffering capacity may be greater in healthy young women compared to men. This abstract was presented at the American Physiology Summit 2025 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.