Analysis of effects of 2,2',5,5'-tetrachlorobiphenyl on the flux control in oxidative phosphorylation system in rat liver mitochondria.

Modular kinetic analysis reveals that the environmental pollutant 2,2',5,5'-tetrachlorobiphenyl (2,2',5,5'-TCB) affects a large number of steps in oxidative phosphorylation in rat liver mitochondria. 2,2',5,5'-TCB increases membrane permeability to ions, and inhibits NADH dehydrogenase, cytochrome bc1, cytochrome oxidase (all in the respiratory chain) and ATP-synthase (in the phosphorylation subsystem). Surprisingly, flux control distribution does not change. A kinetic model for oxidative phosphorylation was used to simulate these findings, and it was found that combined large changes in the processes indicated indeed left the flux control largely unchanged. In addition, computational analysis with the model indicated that the adenine nucleotide translocator might be inhibited by 2,2',5,5'-TCB.