AbstractMitochondrial encephalomyopathies resulting from electron transport chain (ETC) dysfunction can present with a wide spectrum of clinical manifestations having significant neuropathology and a progressive nature. Despite advances in diagnosis of ETC disorders, treatment still remains inadequate. A recent study in fibroblasts and myoblasts revealed the ability of fibrate treatment to correct ETC enzyme deficiencies. Therefore, fibrates may represent potential therapeutic agents to correct the neurological ETC impairment responsible for the encephalopathic presentation of these disorders. Consequently, this study assessed the effect of bezafibrate on human astrocytoma (HA) 1321N cell ETC activity and coenzyme Q10 (CoQ10) status. HA cells were incubated for 72 H with 300 μM or 500 μM bezafibrate and for 7 days with only 500 μM bezafibrate. A significant effect on ETC activity was observed after 7 days incubation with 500 μM bezafibrate yielding a 130% (P < 0.05) increase in complex IV activity, accompanied by a 33% (P < 0.05) increase in cellular ATP level and a 25% (P < 0.001) decrease in extracellular lactate/pyruvate ratio compared to control levels. Following 7 days culture with bezafibrate, the CoQ10 status of the HA cells appeared to increase although this was not found to be significant. The results of this study have indicated evidence of a bezafibrate induced increase in ETC complex IV activity. Further studies are required to assess the ability of bezafibrate treatment to correct neurological ETC impairment in available animal models of ETC dysfunction before the therapeutic efficacy of this pharmacological agent can be further considered in the treatment of the encephalopathic presentation of ETC disorders.