Mitochondrial function and dysfunction in sepsis

Mitochondria are the key source of cellular ATP and their structure and function are markedly affected by pathophysiologic processes associated with the host.s response to invading pathogens. In particular, the highly reactive compound peroxynitrite, generated by the reaction of nitric oxide and superoxide anions, inhibits mitochondrial enzymes and damages lipids, proteins, and nucleic acids. Enhanced oxidative stress induces DNA strand breaks that are repaired by activation of poly(ADP-ribose)polymerase (PARP). This process consumes large amounts of nicotinamide adenine dinucleotide (NAD) leading to cellular NAD depletion that impairs flux of reducing equivalents into the respiratory chain and also further promotes inflammation. In experimental studies, novel therapeutic strategies that aim to ameliorate the host.s pathogen response or to modulate intracellular signaling events related to oxidative stress protected mitochondrial function and preserved cellular respiration ultimately leading to improved organ function.© Springer-Verlag 2010.