Figure 1.

Role for irreversible inhibition of cytochrome c oxidase in neurodegeneration. Peroxynitrite can be formed in astrocytes upon activation. In astrocytes, peroxyntrite irreversibly damages cytochrome c oxidase, which causes mitochondrial dysfunction. However, these cells compensate the energy deficiency by activating glycolysis and survive. Peroxynitrite is a highly diffusible molecule, and hence it reaches neighboring neurons, where it irreversibly damages cytochrome c oxidase. In contrast to astrocytes, neurons cannot up-regulate the energy-compensating glycolysis and hence they die by bioenergetic crisis. Thus, the irreversible inhibition of cytochrome c oxidase by peroxynitrite has a critical negative effect on neuronal survival and may contribute to the propagation of neurodegeneration.