Progress on the mitochondrial permeability transition pore: regulation by complex I and ubiquinone analogs.

This review summarizes recent progress on the regulation of the mitochondrial permeability transition pore, an inner membrane channel that may play a role in cell death. We briefly cover its key control points as emerged over the last few years from studies on isolated mitochondria; and describe in some detail our recent results indicating that the pore is modulated by the respiratory chain complex I and can be specifically blocked by selected ubiquinone analogs. We discuss the potential relevance of these findings for the structural definition of the permeability transition pore and illustrate the pharmacological perspectives they offer in diseases where mitochondrial dysfunction is suspected to play a key role.