Mitochondrial oxidative capacity outpaces redox buffering during endurance training across rat tissues: sex-dimorphic scaling revealed by a thermodynamic framework analysis of MoTrPAC
A secondary analysis of the MoTrPAC rat endurance training dataset (Nature 2024; Cell Metabolism 2024) through the Vandiver–Neufer thermodynamic framework for mitochondrial redox biology. An 85-gene set organized by thermodynamic function (ETS, ATP synthase, NNT, GSH, TRX, SOD), queried across 42,770 observations spanning 19 tissues, 5 omic layers, 4 training time points, and both sexes.
Headline result. After 8 weeks of endurance training, transcriptional investment in redox buffering scales sub-linearly with ETS expansion in both sexes. Males (conservative estimate, excluding two influential tissues): β = 0.55 [0.28, 0.82], R² = 0.57, p = 0.0017. Females (conservative): β = 0.31 [0.10, 0.52], R² = 0.42, p = 2.8 × 10⁻⁶. The pattern replicates at the protein level in an independent omic layer (males β = 0.43, p(β<1) = 7.6 × 10⁻⁴; females β = 0.22, p(β<1) = 4.2 × 10⁻⁵). Sex-dimorphic quality-control architecture: males coordinate ETS with mtUPR and mitophagy (damage-sensing); females through AMPK (energy-sensing).