The targets of 2,2',5,5'-tetrachlorobiphenyl in the respiratory chain of rat liver mitochondria revealed by modular kinetic analysis.

The response of the respiratory subsystem of oxidative phosphorylation to the environmental pollutant, 2,2′,5,5′-tetrachlorobiphenyl (2,2′,5,5′-TCB) was investigated by modular kinetic approach. The effects of 20 μM 2,2′,5,5′-TCB on the activity of the respiratory chain modules in rat liver mitochondria oxidizing succinate (+ rotenone) in state 3 were assessed. The toxin inhibited the rate of respiration by 23%. Analysis around cytochrome c revealed that 2,2′,5,5′-TCB inhibited both cytochrome c-oxidizing and - reducing modules. The toxin inhibited also CoQ-oxidizing module, however it did not affect the kinetics of CoQ-reducing module. Taken together, these data indicated that 2,2′,5,5′-TCB inhibited cytochrome b

Analysis of effects of 2,2',5,5'-tetracholorobiphenyl 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 bcl, 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

Modular kinetic analysis reveals differences in Cd2+ and Cu2+ ion-induced impairment of oxidative phosphorylation in liver.

Impaired mitochondrial function contributes to copper- and cadmium-induced cellular dysfunction. In this study, we used modular kinetic analysis and metabolic control analysis to assess how C

Metabolic control of mitochondrial properties by adenine nucleotide translocator determines palmitoyl-CoA effects.

Inhibition of the mitochondrial adenine nucleotide translocator (ANT) by long-chain acyl-CoA esters has been proposed to contribute to cellular dysfunction in obesity and type 2 diabetes by increasing formation of reactive oxygen species and adenosine via effects on the coenzyme Q redox state, mitochondrial membrane potential (Δψ) and cytosolic ATP concentrations. We here show that 5 μm palmitoyl-CoA increases the ratio of reduced to oxidized coenzyme Q (Q