Mitochondrial mechanisms of sepsis-induced organ failure.

Abstract

Sepsis is the leading cause of death in medical intensive care units. Though progress has been made in the early treatment of sepsis associated with hemodynamic collapse (septic shock), little is known about the pathogenesis of delayed organ dysfunction during sepsis. A growing body of data indicates that sepsis is associated with acute changes in cell metabolism, and that mitochondria are particularly susceptible. The severity of mitochondrial pathology varies according to host and pathogen factors, and appears to correlate with loss of organ dysfunction. In this regard, low levels of cell apoptosis and mitochondrial turnover are normally observed in all metabolically active tissues; however, these homeostatic mechanisms are frequently overwhelmed during sepsis and contribute to cell and tissue pathology. Thus, a better understanding of the mechanisms regulating mitochondrial damage and repair during severe sepsis may provide new treatment options and better outcomes for this deadly disease (30-60% mortality). Herein, we present compelling evidence linking mitochondrial apoptosis pathways to sepsis-induced cell and organ failure and discuss the implications in terms of future sepsis research.