Sulfur dioxide (SO2) is a common environmental pollutant. Mitochondria play essential roles in energy metabolism, generation of reactive oxygen species, and regulation of apoptosis in response to neuronal brain injury. It is of interest to observe the effect of SO2 on mitochondrial function in brain. In the present study, male Wistar rats were housed in exposure chambers and treated with 3.5, 7 and 14 mg/m(3) SO2 for 4 h/day for 30 days, while control rats were exposed to filtered air in the same condition. Mitochondrial membrane potential (MMP) was assessed in cerebral mitochondria using the lipophilic cationic probe JC-1. The amount of ATP was measured by the luciferinluciferase method. Analyses of mitochondrial replication and transcription were performed by real time PCR. The protein levels were detected using Western blotting. Our results showed that cerebral mtDNA content was markedly increased in rats after SO2 exposure. Paralleling the change in mtDNA content, MMP, ATP content, MDA level, CO1 & 4 and ATP6 & 8 expression, and cytochrome c oxidase activity were increased in rat cortex after SO2 inhalation. Moreover, mitochondrial biogenesis was accompanied by increased expression of NRF1 and TFAM, whereas PGC-1 alpha was not changed. We report for the first time increased mitochondrial biogenesis in brain of rats exposed to SO2, which might be an adaptive response to mitochondrial depletion by oxidant damage. (c) 2012 Elsevier Ireland Ltd. All rights reserved.