André Augusto Corsetti Martins, Clara Rodrigues Ferreira¹, Ana Paula Pereira da Silva, Laudiene Evangelista Meyer e Antonio Galina ^1¶

The alkylating agent 3-Bromo-pyruvate (3-BrPyr) has been suggested to be used as an anti-tumoral drug based on its anti-proliferative property in hepatoma cells. This effect has been proposed to occur by disturbance of glycolysis leading to a decreased rate of ATP synthesis. The main target of inhibition of 3-BrPyr is believed to be the hexokinase type II (HK) of tumor cells. Nevertheless, 3-BrPyr was also described to inhibit the oxygen consumption in hepatoma cells. Despite of this observation, the detailed mechanism of action of 3-BrPyr in mitochondrial respiration in normal and tumor cells is unknown. The aim of this study was to investigate the effect of 3-BrPyr on mice liver mitochondria electron transport chain (ETC) and the F_oF₁-ATP synthase activities. The ATPase activity of F_oF₁-ATP synthase was only partially inhibited (25 %) by 1 mM 3-BrPyr. Interestingly, 3-BrPyr was much more effective to inhibit respiration. The detailed analysis of the respiratory complexes of ETC revealed that the membrane potential (DYm) was affected when succinate was added to the respiratory medium. 3-BrPyr caused an inhibition of DYm formation at concentrations above 500 mM. Higher concentrations of 3-BrPyr caused a complete inhibition of DYm by succinate without effect on DYm formation by ascorbate/TMPD (an electron donors of complex IV).