PFOS and GenX Induce Mitochondrial Toxicity and Differentially Alter Respiratory Complex Activities in Liver and Brain

PFOS and GenX exposure in mouse liver and brain mitochondria inhibits respiratory Complex III and IV activities, with combined treatment generally causing greater inhibition than either compound alone.

• Why it matters: PFAS are linked to adverse health outcomes, but how individual PFAS and mixtures affect mitochondrial respiratory function across exposure durations and tissues is not well defined.
• What they did: Acute effects were tested in isolated mouse liver and brain mitochondria, while repeated dosing used mice given PFOS, GenX, or their mixture at 0.2, 2, or 10 mg/kg for 1 month or 0.2 mg/kg for 5 months, alongside PFAS distribution, OXPHOS protein expression, and docking predictions for Complexes III and IV.
• The result: Across acute, sub-chronic, and chronic regimens, mitochondrial responses were exposure-dependent and tissue-specific, including more pronounced liver complex reductions after sub-chronic dosing and selected brain complex changes after chronic low-dose exposure, with PFAS distribution and region-specific OXPHOS protein variation supporting these effects.

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