Targeted delivery of mitochondrial protectors prevents cardiolipin oxidation and cell degeneration following brain trauma or radiation injury

Abstract

Reactive oxygen species (ROS) produced by injured cell powerhouses, mitochondria may lead to the development of heavy neuronal disorders of both chronic (Alzheimer disease, Parkinson disease, etc.) and acute brain injury followed by a secondary neuronal damage and death over time. Once a mitochondrion is injured, a phospholipid constituent of its inner membrane, cardiolipin (CL) undergoes externalization triggering a sequence of events which may lead to either natural elimination of injured mitochondria without the host cell injury or programmed host cell suicide, apoptosis. Mitochondria-induced apoptosis is, among other, also responsible for radiation-induced damage of radiosensitive organs like bone marrow and the small intestine. In order to prevent cell suicide, (per)oxygenation of externalized CL at the outer side of the inner mitochondrial membrane catalyzed by the cytochrome c/CL complex should be suppressed. Here some approaches that lead to the targeted suppression of ROS and inhibition of cyt c/CL complex (per)oxygenative activity within mitochondria are discussed, which provide the basis for the development of new anti-apoptotic drugs defending the neuronal and other tissues from degeneration by ROS. The positive effects of these drugs were demonstrated in the laboratory animals developing secondary neuronal damage over time following traumatic brain injury or suffering from radiation-induced disorders.