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

Abstract

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 50–1000 μM PFOA for 10 min. 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 1 mM and MMP showed a decreasing trend at 500 μM and 1 mM, 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.