title: The effects of sepsis on mitochondria.
abstract: BACKGROUND
  Sepsis is associated with mitochondrial dysfunction and impaired oxygen consumption, which may condition clinical outcome independent of tissue oxygenation. However, mitochondrial role in sepsis severity remains unknown. We aimed to characterize mitochondrial function in sepsis, establish its origin and cellular consequences, and determine its correlation with clinical symptoms and outcome.
  
  
  METHODS
  Different markers of mitochondrial activity, nitrosative and oxidative stress, apoptosis, and inflammation were measured in peripheral blood mononuclear cells (PBMCs) and plasma of 19 septic patients and 20 controls. Plasma capacity to induce mitochondrial dysfunction was assessed in muscle mitochondria from 5 healthy individuals incubated with plasma of septic patients or controls.
  
  
  RESULTS
  Despite unaltered mitochondrial mass and protein synthesis, enzymatic mitochondrial complexes I, III, and IV and oxygen consumption were significantly inhibited in sepsis. Septic plasma tended to reduce oxygen consumption of healthy mitochondria and showed significantly increased amounts of extracellular mitochondrial DNA and inflammatory cytokines, especially in patients presenting adverse outcome. Active nuclear factor kappa-light-chain enhancer of activated B cells (NFKB) was also significantly increased, together with nitric oxide, oxidative stress and apoptosis. Additionally, sepsis severity significantly correlated with complex I inhibition, NFKB activation and intercellular adhesion molecule expression.
  
  
  CONCLUSIONS
  A plasmatic factor such as nitric oxide, increased in inflammation and able to induce mitochondrial dysfunction, oxidative stress and apoptosis, may be responsible for cell damage in sepsis. Together with bacterial infection, leakage of mitochondrial DNA from damaged cells into circulation could contribute to systemic inflammatory response syndrome. Mitochondrial dysfunction and inflammation correlate with sepsis severity and outcome, becoming targets for supporting therapies.
authors.affiliation: Mitochondrial Research Laboratory, IDIBAPS, University of Barcelona, Internal Medicine Department, Hospital Clínic of Barcelona (HCB, Barcelona) and Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER, Valencia). garrabou@clinic.ub.es
authors.forename: Glòria
authors.initials: G
authors.lastname: Garrabou
authors.forename: Constanza
authors.initials: C
authors.lastname: Morén
authors.forename: Sònia
authors.initials: S
authors.lastname: López
authors.forename: Ester
authors.initials: E
authors.lastname: Tobías
authors.forename: Francesc
authors.initials: F
authors.lastname: Cardellach
authors.forename: Oscar
authors.initials: O
authors.lastname: Miró
authors.forename: Jordi
authors.initials: J
authors.lastname: Casademont
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D017209:Apoptosis; D002478:Cells, Cultured; D016207:Cytokines / Q000097:blood; D004272:DNA, Mitochondrial / Q000097:blood; D042967:Electron Transport Complex I; D014450:Electron Transport Complex III / Q000378:metabolism; D003576:Electron Transport Complex IV / Q000378:metabolism; D005260:Female; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000378:metabolism / Q000502:physiology; D008297:Male; D008875:Middle Aged; D008928:Mitochondria / Q000502:physiology*; D016328:NF-kappa B / Q000378:metabolism; D009569:Nitric Oxide / Q000097:blood; D018384:Oxidative Stress; D010101:Oxygen Consumption; D018805:Sepsis / Q000473:pathology* / Q000503:physiopathology*
chemical_list: D016207:Cytokines; D004272:DNA, Mitochondrial; D016328:NF-kappa B; D009569:Nitric Oxide; D003576:Electron Transport Complex IV; D042967:Electron Transport Complex I; D014450:Electron Transport Complex III