Alterations of mitochondrial function in sepsis and critical illness.
OBJECTIVE
Septic shock is the consequence of a conflict between a pathogenic agent and the immune system of the host. This conflict induces an immune-mediated cytokine storm, with a whole-body inflammatory response often leading to multiple organ failure. Although extensively studied, the pathophysiology of sepsis-associated multiorgan failure remains unknown. One postulated mechanism is changes in mitochondrial function with an inhibition of mitochondrial respiratory chain and a decrease of oxygen utilization.


RESULTS
Mitochondrion is a key organelle in supplying energy to the cell according to its metabolic need. Hypoxia and a number of the mediators implicated in sepsis and in the associated systemic inflammatory response have been demonstrated to directly impair mitochondrial function. A large body of evidence supports a key role of the peroxynitrite, which can react with most of the components of the electron transport chain, in the mitochondrial dysfunction.


CONCLUSIONS
A pivotal role is suggested for mitochondrial dysfunction during the occurrence of multiorgan failure. Understanding the precise effect of sepsis on the mitochondrial function and the involvement of mitochondria in the development of multiple organ failure is fundamental. More human studies are thus necessary to clarify the mitochondrial dysfunction in the various phases of sepsis (early and late phase) before testing therapeutic strategies targeting mitochondria.
Harrois
Anatole
A
Département d'Anesthésie-Réanimation, AP-HP, Université Paris Sud XI, Hôpital Bicêtre, Le Kremlin-Bicêtre, France.
Huet
Olivier
O
Duranteau
Jacques
J
D016638:Critical Illness; D006801:Humans; D008928:Mitochondria / Q000502:physiology*; D028361:Mitochondrial Diseases / Q000209:etiology* / Q000276:immunology / Q000503:physiopathology; D009102:Multiple Organ Failure / Q000209:etiology* / Q000276:immunology / Q000503:physiopathology; D012772:Shock, Septic / Q000150:complications* / Q000276:immunology / Q000503:physiopathology