Prevention of cell damage in ischaemia: novel molecular targets in mitochondria

Abstract

Ischaemia results in a decrease of blood supply to an organ. It may be sudden or progressive, partial or complete. In any case, the lack of oxygen induces a decrease in ATP generation followed by a reduction of cellular energy-dependent processes. When ischaemia is followed by a reperfusion, the efflux of oxygen in an anoxied organ promotes an excess of reactive oxygen species (ROS) generation, which impairs the restoration of ATP synthesis. Both effects induce cellular alterations that can lead to cell death in both necrotic and apoptotic forms. As ATP synthesis and ROS generation both occur in mitochondria, they are obvious targets for pharmacological interventions aiming to prevent or block deleterious effects induced by a lack of oxygen. Different approaches may be used according to the state of the pathological process under investigation. In general, prevention of the ischaemic process is more successful than the cure of the following reperfusion state. This review summarises pharmacological strategies designed to improve cellular protection before or during ischaemia–reperfusion acting via the mitochondria and highlights promising new mitochondrial targets to be considered for future therapies.

• Bcl-2
• Ca²⁺
• carbohydrates
• ischaemia
• lipids
• mitochondria
• oxidative stress
• permeability transition pore
• stroke