ИСТИНА

To elucidate whether perturbation in mitochondrial processes could induce p53 tumor suppressor response, we inhibited each of the mitochondrial electron transport chain complexes and monitored intracellular levels and transcriptional activity of p53. We found that inhibitors of electron transport chain complexes I and IV that interfere with mitochondrial respiration, as well as uncoupling reagents that reduce mitochondrial membrane potential, were not capable of inducing p53 response. However, strong activation of p53 ultimately resulting in p53-dependent apoptosis was observed after treatment with specific inhibitors of electron transport chain complex III. Our recent insight in the signaling pathways connecting inhibition of mitochondrial cytochrome bc1 complex with p53 activation will be discussed.