Mitochondrial role in sepsis progression

CARRERAS MC

Buenos Aires

Congreso; VIII Meeting of the Society for Free Radical Biology and Medicine-South American Group; 2013

Society for Free Radical Biology and Medicine-South American Group

Mitochondrial derangements and the subsequent disruption in energy metabolism are associated with multiple organ failure, and an increased mortality in critically ill patients. Nitric oxide (NO) is an important element of host defense, a central component of innate immunity, and an effective antimicrobial agent. Large amounts of NO and peroxynitrite (ONOO-), among other factors, are implicated as mediators for the late phase of hypotension, apoptosis, lactic acidosis, and multiple organ failure in septic or endotoxic shock. Oxidative and nitrosative stress, which occurs within the mitochondria during sepsis, can damage mitochondrial proteins, phospholipids, and mtDNA. The protection of mitochondrial integrity and quality is the task of cellular programs that monitor and replace dysfunctional mitochondria with new organelles. These programs require the transcription and replication of mitochondrial DNA, mitochondrial protein synthesis, mitochondrial fusion and fission, mitochondrial autophagy, and mitochondrial proliferation, as well as reorganization of the cytoskeleton. We observed that the imbalance of mitochondrial fusion and fission resulted in mitochondrial fragmentation and apoptosis that accompanied the progression of sepsis in two experimental models (endotoxemia and fecal peritonitis).