Mitochondrial function in sepsis: acute phase versus multiple organ failure.
OBJECTIVE
To describe temporal changes in mitochondrial function during the septic process, including the recovery phase.


METHODS
Literature review.


METHODS
Clinical studies and laboratory models.


RESULTS
Biochemical and ultrastructural mitochondrial abnormalities have been recognized in in vivo, ex vivo, and in vitro laboratory models of sepsis for >30 yrs. Short-term models show variable effects on mitochondrial function and structure; this is likely related to differences in model design, including species, organs studied, degree of septic insult, and degree of resuscitation. Longer-term models more consistently reveal mitochondrial dysfunction and damage. There is a rebound increase in oxygen consumption and resting energy expenditure in the recovery phase of sepsis. This could reflect mitochondrial recovery (biogenesis) that may restore the energy supply needed to fuel restorative metabolic processes and enable patient survival.


CONCLUSIONS
Mitochondrial dysfunction seems to be intrinsically involved in the pathogenesis of multiple organ failure. As a consequence of a progressive decrease in energy availability, metabolism must decrease or the cell will die. The interplay between adenosine 5'-triphosphate supply and demand, dictated by the degree of mitochondrial dysfunction and the level of metabolic shutdown (analogous to a hibernation-type response), seems to be crucial in determining outcome. Further studies are needed to confirm this hypothesis.
Singer
Mervyn
M
Intensive Care Medicine, Bloomsbury Institute of Intensive Care Medicine, Department of Medicine, University College London, London, UK. m.singer@ucl.ac.uk
D000208:Acute Disease; D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D004734:Energy Metabolism; D006801:Humans; D008928:Mitochondria / Q000378:metabolism* / Q000648:ultrastructure; D009102:Multiple Organ Failure / Q000378:metabolism*; D010101:Oxygen Consumption; D018805:Sepsis / Q000378:metabolism*
D000255:Adenosine Triphosphate