Skeletal Muscle Mitochondrial Function and Mitochondria-related Protein Expression in Men and Women During Acute Exercise-Heat Stress and Acclimation

Abstract

INTRODUCTION: Military personnel can exhibit improved performance and reduced physiological strain in hot environments with the induction of heat adaptations. Mild heat exposure at 40°C heat serves therapeutic purposes, enhancing metabolic flexibility, and promoting positive muscle adaptations. Research indicates that heat acclimation (HA) leads to increased mitochondrial biogenesis and reduced reactive oxygen species in skeletal muscle, improving thermal tolerance. However, understanding sex differences in mitochondrial function and related protein expression affected by heat acclimation remain limited. Therefore, this study aimed to explore mitochondrial respiration and the expression of mitochondria-related proteins to better understand the impact of heat stress on mitochondrial adaptations in skeletal muscle in both males and females. METHODS: Healthy men (M:n = 7, 22±2yo, VO2max 52.86±2.35ml·kg−1·min−1) and women (F:n = 7, 24±1yo, VO2max 45.97±2.57 ml·kg−1·min−1) participated in a 5-day heat acclimation (HA) at 40°C and 40% relative humidity. Before and after HA, participants completed a heat tolerance test (HTT) measuring time to reach a rectal temperature of 39.5°C or volitional failure. Biopsies from the vastus lateralis were taken immediately post-HTT for musculoskeletal analysis. Mitochondrial respiratory function was assessed using Oroboros O2K, employing high-resolution respirometry. Paired sample t-tests were used to determine statistical significance between groups (p<0.05). Proteomics data were mined for Gene Ontology (GO) terms related to mitochondrial function (STRING V.12.0) (adjusted p<0.05). RESULTS: Both men and women exhibited significant enhancements in complex I-mediated respiration and complex I+II maximal coupled respiration after HA (PRE-HA: M:P=0.009, P=0.026; F:P=0.016, P=0.011). No sex differences in mitochondria respiration were observed before or after HA. Before HA, skeletal muscle from women showed higher expression in 4 proteins (ND61, NDUFB1, COX1, ATP5MF) associated with 9 GO terms related to mitochondrial function compared to men. However, after HA, men exhibited higher expression in 14 proteins (MTX2, APOOL, DNAJC11, TIMM13, NDUFAB1, DNAJC11, MAVS, CHCHD4, NDUFAF4, ATP5PF, NDUFAS, UQCRH, SSBP1, ND3) associated with 21 mitochondria-related GO terms compared to women. CONCLUSION: Acclimation to heat stress is associated with positive mitochondrial adaptation in both men and women. Although enhancements in mitochondrial respiratory function in both men and women after HA, there were different skeletal muscle responses between men and women regarding the regulation of mitochondria-related proteins after a bout of exercise-heat stress. Funding: DoD BA200299. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.