[Pathomechanisms of organ failure. Mitochondrial dysfunction in sepsis].
Proinflammatory mediators as well as increased formation of reactive oxygen and nitrogen species impair cellular respiration during sepsis. In particular, the highly reactive peroxynitrite irreversibly damages lipids, proteins and nucleic acids and also inhibits enzyme complexes of the respiratory chain. In this way cellular metabolic functions and subsequently organ functions are also impaired. Repair of DNA by poly(ADP-ribose)polymerase consumes large amounts of nicotinamide adenine dinucleotide (NAD+) which leads to cellular NAD+ depletion further promoting inflammation. This article summarizes central aspects of the pathophysiology of mitochondrial dysfunction during sepsis and gives an overview about newly developed strategies which proved effective in experimental studies and may have a potential clinical application in the future.
Wendel
M
M
Institut für Physiologie, Medizinische Fakultät Carl Gustav Carus, TU Dresden, Fiedlerstr. 42, 01307, Dresden, Deutschland. MartinaWendel@gmx.de
Heller
A R
AR
Koch
T
T
D004247:DNA / Q000235:genetics; D005609:Free Radicals / Q000378:metabolism; D006801:Humans; D018836:Inflammation Mediators / Q000502:physiology; D008928:Mitochondria / Q000201:enzymology / Q000473:pathology / Q000648:ultrastructure; D028361:Mitochondrial Diseases / Q000201:enzymology / Q000209:etiology / Q000473:pathology*; D009102:Multiple Organ Failure / Q000201:enzymology / Q000209:etiology / Q000473:pathology*; D018805:Sepsis / Q000150:complications / Q000473:pathology*
D005609:Free Radicals; D018836:Inflammation Mediators; D004247:DNA