Protein S-glutathionylation and sex dimorphic effects on hydrogen peroxide production by dihydroorotate dehydrogenase in liver mitochondria

Fatty acid oxidation drives hydrogen peroxide production by α-ketoglutarate dehydrogenase

“…Using different substrate and inhibitor combinations and transgenic mouse models, we had previously shown in several studies PDH and KGDH display rates for mH 2 O 2 generation that can be up to ∼6-fold higher in male liver mitochondria when compared to the female littermates (Gill et al , 2020; Mallay et al , 2019; Wang et al ., 2023). This was also the case for dihydroorotate dehydrogenase (DHODH), an oxidoreductase embedded in the mitochondrial inner membrane that is required for pyrimidine biosynthesis (Koufos & Mailloux, 2023). In the present study, we found rates of mH 2 O 2 generation were significantly lower in female liver mitochondria when compared to males.…”

Mitochondrial hydrogen peroxide production by pyruvate dehydrogenase and α-ketoglutarate dehydrogenase in oxidative eustress and oxidative distress

“…The sex dimorphic effect in PSSG adduct formation in liver mitochondria was related to differences in redox tone and mH 2 O 2 buffering capacity ( 80 , 108 ). Indeed, liver mitochondria from female rodents and humans have greater antioxidant capacity and redox tone, better mitochondrial coupling between nutrient oxidation and ATP production, and increased proton leaks, which reduces protonic backpressure to limit ROS production ( 11 , 108 , 109 ).…”