Pathophysiological implications of mithochondrial cell death control.

Abstract

Mitochondria are not only the cell's powerhouse; they also constitute the weapon store for cellular suicide. In response to multiple distinct insults, mitochondrial membranes are permeabilized in a highly regulated fashion. Mitochondrial outer membrane permeabilization results in the cytosolic release of several factors that are normally secluded within the mitochondrial intermembrane space. Once in the cytosol, these factors act as (or activate) catabolic hydrolases that digest of the cell's content, thus causing cell death and facilitating the subsequent corpse removal. Multiple lethal signal transduction molecules, toxins and experimental anticancer agents can induce mitochondrial membrane permeabilization, a property that is taken advantage for tumour therapy. Conversely, some pharmacological agents have been designed to inhibit mitochondrial membrane permeabilization and can be used for the experimental avoidance of unwarranted cell death, for instance in stroke or myocardial infarction. Altogether, it appears that mitochondrial cell death control has wide physiological, pathological and pharmacological implications.