In the previous issue of Critical Care, Donnino and
colleagues [1] suggest a coenzyme Q
10
(CoQ
10
) deficiency
in patients with septic shock. Tis study provides new
insights into the field of oxidative stress and mitochon-
drial dysfunction during septic shock. Tough extensively
studied, the pathophysiology of sepsis-associated multi-
organ failure (MOF) remains unknown. Sepsis is charac-
terized by a systemic dysregulated inflammatory res-
ponse and oxidative stress. One postulated mechanism is
a set of changes in mitochondrial function with an
inhibition or a dysfunction of the mitochondrial respira-
tory chain and a decrease of oxygen use [2]. A large body
of evidence supports a key role of excessive production of
reactive oxygen species in mitochondrial dysfunction and
cellular injury during the various phases of sepsis (early-
and late-phase MOF) [3,4]. Understanding the precise
effect of sepsis on the mitochondrial function and the
involvement of mitochondria in the development of
MOF is fundamental.
CoQ
10
, also known as ubiquinone, plays a crucial role in
the mitochondrial respiratory chain for ATP production.
CoQ
10
is a lipophilic mobile electron carrier that is
located in the inner mitochondrial membrane. CoQ
10
receives electrons from complex I (NADH dehydroge-
nase) and complex II (succinate dehydrogenase) (reduc-
tion of ubiquinone to ubiquinol). Complex III (coenzyme
Q-cytochrome c reductase) accepts electrons from
ubiquinol and passes them to cytochrome c. CoQ
10
has
been reported to have the ability to act as an effective
antioxidant. Ubiquinone prevents peroxidation damage
to cell membranes, regenerates α-tocopherol, and main-
tains thiol levels. CoQ
10
is also a cofactor for uncoupling
proteins. Finally, CoQ
10
plays a role in the control of
mitochondrial transition pore opening, which is involved
in apoptosis.
Several studies suggest an important role of CoQ
10
deficiency in neurodegenerative conditions such as Par-
kinson disease, Friedreich ataxia, and Huntington chorea
and a benefit of oral supplementation [5]. In addition,
CoQ
10
deficiency could play a role in the pathogenesis of
heart failure. Recently, McMurray and colleagues [6]
reported that a low serum CoQ
10
concentration was
associated with worse outcomes in heart failure. It is
important to note that, in that study, CoQ
10
was a marker
of more advanced disease but that low plasma coenzyme
CoQ
10
was not an independent predictor of prognosis.
So if there is a deficit in CoQ
10
during sepsis, the drug
could be used in the prevention and treatment of sepsis-
associated MOF to boost mitochondrial function and to
mitigate cellular damage caused by oxidative stress. Until
now, only animal models have been used to test the impact
of CoQ
10
on the consequences of sepsis. Injection of CoQ
10
into the rostral ventrolateral medulla (medullary origin of
sympathetic vasomotor tone) of rats diminished mortality
and lipopolysaccharide-induced hypotension during
exposure to lipopolysaccharide [7]. Lowes and colleagues
[8] reported that MitoQ, an antioxidant this is selectively
targeted to mitochondria and that comprises the lipophilic
triphenylphosphonium cation covalently bound to ubiqui-
nol, was able to limit oxidative stress, maintain the mito-
chondrial membrane potential, and prevent mitochondrial
damage (endothelial cell model of sepsis) and acute liver
and renal dysfunction (rat model of sepsis). In rat and
mouse models of sepsis induced by endotoxin injected
intraperitoneally, Supinski and colleagues [9] demon-
strated that MitoQ prevented endotoxin-induced reduc-
tions in cardiac pressure-generating capacity, systolic
Abstract
Donnino and colleagues provide new insights into the
feld of oxidative stress and mitochondrial dysfunction
during septic shock. These authors suggest a coenzyme
Q
10
(CoQ
10
) defciency in patients with septic shock.
Larger prospective observational trials measuring CoQ
10
in patients with septic shock are required to confrm the
possibility of CoQ
10
depletion. This study is a new step
toward a study testing CoQ
10
as a potential therapeutic
agent for patients with septic shock.
© 2010 BioMed Central Ltd
Coenzyme Q
10
defciency in septic shock patients
Laurent Dupic
1
, Olivier Huet
2,3
and Jacques Duranteau*
3
See related research by Donnino et al., http://ccforum.com/content/15/4/R189
COMMENTARY
*Correspondence: jacques.duranteau@bct.aphp.fr
3
Assistance Publique - Hôpitaux de Paris, Hôpital Bicêtre, Département
d’Anesthésie-Réanimation, EA 3509 Université Paris Sud XI, France F-94275,
Le Kremlin-Bicêtre, France
Full list of author information is available at the end of the article
Dupic et al. Critical Care 2011, 15:194
http://ccforum.com/content/15/5/194
© 2011 BioMed Central Ltd