Sex-specific differences in mitochondrial function and free radical homeostasis
are reported in the context of aging but not well-established in pathogeneses
occurring early in life. Here, we examine if sex disparity in mitochondria
function, morphology, and redox status starts early and hence can be implicated
in sexual dimorphism in cardiac as well as neurological disorders prevalent
at young age. Although mitochondrial activity in the heart did not
significantly vary between sexes, female brain exhibited enhanced respiration
and higher reserve capacity. This was associated with lower H2O2 production
in female cardiac and brain tissues. Using transmission electron microscopy,
we found that the number of female cardiac mitochondria is moderately
greater (117
3%, P = 0.049, N = 4) than male’s, which increased significantly
for cortical mitochondria (134
4%, P = 0.001, N = 4). However,
male’s cardiac mitochondria exhibited fragmented, circular, and smaller mitochondria
relative to female’s mitochondria, while no morphologic sex-dependent
differences were observed in cortical mitochondria. No sex differences
were detected in Nox2 and Nox4 proteins or O2-consuming/H2O2-producing
activities in brain homogenate or synaptosomes. However, a strong trend of
increased EPR-detected NOX superoxide in male synaptosomes hinted at
higher superoxide dismutase activity in female brains, which was confirmed
by two independent protocols. We also provide direct evidence that respiring
mitochondria generally produce an order-of-magnitude lower reactive oxygen
species (ROS) proportions than currently estimated. Our results indicate that
sex differences in mitochondrial biogenesis, bioenergetics, and morphology
may start at young age and that sex-dependent SOD capacity may be responsible
for differences in ROS homeostasis in heart and brain.