tailieunhanh - Báo cáo Y học: Bax-induced cell death in yeast depends on mitochondrial lipid oxidation

The oxidant function of pro-apoptotic protein Bax was investigated through heterologous expression in yeast. Direct measurements of fatty acid content show that Bax-expression induces oxidation of mitochondrial lipids. This effect is prevented by the coexpression of Bcl-xL. The oxi-dation actually could be followed on isolated mitochondria as respiration-induced peroxidation of polyunsaturatedcis-parinaric acid and on whole cells as the increase in the amount of thiobarbituric acid-reactiveproducts. . | Eur. J. Biochem. 269 Mdí 22002 FEBS 2002 doi Bax-induced cell death in yeast depends on mitochondrial lipid oxidation Muriel Priault 1 Jean-Jacques Bessoule2 Angela Grelaud-Coq1 Nadine Camougrand1 and Stephen Manon1 1UMR5095 de Bordeaux 2 Bordeaux France 2UMR5544 de Bordeaux 2 Bordeaux France The oxidant function of pro-apoptotic protein Bax was investigated through heterologous expression in yeast. Direct measurements of fatty acid content show that Bax-expression induces oxidation of mitochondrial lipids. This effect is prevented by the coexpression of Bcl-xL. The oxidation actually could be followed on isolated mitochondria as respiration-induced peroxidation of polyunsaturated cis-parinaric acid and on whole cells as the increase in the amount of thiobarbituric acid-reactive products. Treatments that increase the unsaturation ratio of lipids making them more sensitive to oxidation increase kinetics ol Bax-índuced death. Conversely inhibitors of lipid oxidaiion nnd treatments that decrease the unsaturation ratio of fatty acids decrease kinetics of Bax-induced death. Taken together these results show that Bax-induced mitochondrial lipid oxidation is relevant to Bax-induced cell death. Conversely lipid oxidation is poorly related to the massive Bax-induced superoxide and hydrogen peroxide accumulation which occurs at the same time as chemical or enzymatic sca vengi ng of ROS does not prevent lipid oxidation nor has any effects on kinetics of Bax-induced cell death. Whatever the origin of mitochondrial lipid oxidation these data show that it represents a major step in the cascade of events leading to Bax-induced cell death. These results are discussed in the light of the role of lipid oxidation both in mammalian apoptosis and in other forms of cell death in other organisms. Keywords Bax apoptosis ROS lipid oxidation yeast mitochondria. Apoptosis is a cellular death program involved in .