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

This review summarizes recent progress on the regulation of the mitochondri al 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 ub iquinone analogs. We discuss the potential relevance of these findings for the structural definition of the permeability transition pore and illustrat e the pharmacological perspectives they offer in diseases where mitochondri al dysfunction: is suspected to play a key role.