Perfluorooctanoic acid alters mitochondrial bioenergetics and redox status in isolated mouse liver mitochondria

Perfluorooctanoic acid (PFOA) is a persistent environmental pollutant linked to metabolic diseases, wherein mitochondrial dysfunction plays a critical role. This study investigated the direct effects of PFOA on isolated liver mitochondria from male and female mice exposed to 50-1,000μM PFOA for 10min. We assessed mitochondrial respiratory complex (CI-CIV) activities, ATP production, oxidative stress markers, and mitochondrial membrane potential (MMP). PFOA selectively altered CII and CIV activities, while CI and CIII remained largely unaffected. Notably, CIV activity increased at higher concentrations, while ATP production decreased at 1mM and MMP showed a decreasing trend at 500μM and 1mM, consistent with impaired mitochondrial energy coupling. Furthermore, ROS/RNS levels showed an increasing trend with increasing PFOA concentrations. Male- and female-derived mitochondria showed different response patterns across several endpoints. GSH levels showed no consistent concentration-dependent pattern, SOD activity showed no statistically significant changes, and cytochrome c levels showed no statistically significant changes under the present experimental conditions. These findings suggest that PFOA directly alters mitochondrial bioenergetic and redox-related processes, consistent with impaired energy coupling and altered redox status.