PMID- 22180620
OWN - NLM
STAT- MEDLINE
DCOM- 20120306
LR  - 20211008
IS  - 1537-6613 (Electronic)
IS  - 0022-1899 (Linking)
VI  - 205
IP  - 3
DP  - 2012 Feb 1
TI  - The effects of sepsis on mitochondria.
PG  - 392-400
LID - 10.1093/infdis/jir764 [doi]
AB  - 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.
FAU - Garrabou, Gloria
AU  - Garrabou G
AD  - Mitochondrial Research Laboratory, IDIBAPS, University of Barcelona, Internal 
      Medicine Department, Hospital Clinic of Barcelona (HCB, Barcelona) and Centro de 
      Investigacion Biomedica en Red de Enfermedades Raras (CIBERER, Valencia). 
      garrabou@clinic.ub.es
FAU - Moren, Constanza
AU  - Moren C
FAU - Lopez, Sonia
AU  - Lopez S
FAU - Tobias, Ester
AU  - Tobias E
FAU - Cardellach, Francesc
AU  - Cardellach F
FAU - Miro, Oscar
AU  - Miro O
FAU - Casademont, Jordi
AU  - Casademont J
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20111216
PL  - United States
TA  - J Infect Dis
JT  - The Journal of infectious diseases
JID - 0413675
RN  - 0 (Cytokines)
RN  - 0 (DNA, Mitochondrial)
RN  - 0 (NF-kappa B)
RN  - 31C4KY9ESH (Nitric Oxide)
RN  - EC 1.9.3.1 (Electron Transport Complex IV)
RN  - EC 7.1.1.2 (Electron Transport Complex I)
RN  - EC 7.1.1.8 (Electron Transport Complex III)
SB  - IM
MH  - Aged
MH  - Aged, 80 and over
MH  - Apoptosis
MH  - Cells, Cultured
MH  - Cytokines/blood
MH  - DNA, Mitochondrial/blood
MH  - Electron Transport Complex I
MH  - Electron Transport Complex III/metabolism
MH  - Electron Transport Complex IV/metabolism
MH  - Female
MH  - Humans
MH  - Leukocytes, Mononuclear/metabolism/physiology
MH  - Male
MH  - Middle Aged
MH  - Mitochondria/*physiology
MH  - NF-kappa B/metabolism
MH  - Nitric Oxide/blood
MH  - Oxidative Stress
MH  - Oxygen Consumption
MH  - Sepsis/*pathology/*physiopathology
EDAT- 2011/12/20 06:00
MHDA- 2012/03/07 06:00
CRDT- 2011/12/20 06:00
PHST- 2011/12/20 06:00 [entrez]
PHST- 2011/12/20 06:00 [pubmed]
PHST- 2012/03/07 06:00 [medline]
AID - jir764 [pii]
AID - 10.1093/infdis/jir764 [doi]
PST - ppublish
SO  - J Infect Dis. 2012 Feb 1;205(3):392-400. doi: 10.1093/infdis/jir764. Epub 2011 
      Dec 16.