Physiopathologie mitochondriale et syndrome septique

Mitochondria are involved in many cellular functions including ATP production, steroids and heme synthesis, thermogenesis, calcium handling, ROS production and apoptosis. During sepsis, mitochondria may be unable to adequately use oxygen and such cytopathic hypoxia may participate to organ failure and death. Mitochondrial morphological abnormalities and dysfunction have been reported in many studies. Sepsis induces reductions in the activities of enzymes such as pyruvate deshydrogenase (which allows pyruvate transfert) and aconitase (Krebs cycle). Stage 3 respiration (with ADP) of mitochondria is reduced while stage 4 (without ADP) is typically increased suggesting uncoupling. Mitochondrial dysfunction is also associated with reductions in respiratory complex content, which has been related to major alteration in the mitochondrial autophagy-biogenesis balance.