Mitochondrial dysfunction, bioenergetic impairment, and metabolic down-regulation in sepsis.
Mitochondrial dysfunction is thought to play an important role in the pathogenesis of many different disease states. It has been proposed that an acquired defect in oxidative phosphorylation prevents cells from using molecular oxygen for adenosine triphosphate production and potentially causes sepsis-induced organ dysfunction. This concept, termed cytopathic hypoxia, however, has been difficult to prove because impaired oxidative phosphorylation has never been shown to cause sepsis-induced organ failure or to be a reversible phenomenon. Presented here is are view of oxidative phosphorylation, evidence of defective electron-transport-chain function in the heart and other organ systems during sepsis, and support for a link between mitochondrial dysfunction and pathologic metabolic down-regulation.
Levy
Richard J
RJ
Department of Anesthesiology and Critical Care Medicine, The Children's Hospital of Philadelphia, University of Pennsylvania, Pennsylvania 19104-4283, USA. levyri@email.chop.edu
D000818:Animals; D015536:Down-Regulation; D004579:Electron Transport; D004734:Energy Metabolism; D015870:Gene Expression; D006605:Hibernation / Q000502:physiology; D006801:Humans; D008928:Mitochondria / Q000378:metabolism*; D009206:Myocardium / Q000378:metabolism; D010085:Oxidative Phosphorylation; D018805:Sepsis / Q000235:genetics / Q000378:metabolism*