[Mitochondrial dysfunction during sepsis, impact and possible regulating role of hypoxia-inducible factor-1alpha]

Regueira, T; Andresen, M; Djafarzadeh, S (2009). [Mitochondrial dysfunction during sepsis, impact and possible regulating role of hypoxia-inducible factor-1alpha]. Medicina intensiva, 33(8), pp. 385-92. Madrid: IDEPSA, International de Ediciones y Publicaciones, S.A. 10.1016/j.medin.2008.10.002

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There is a direct correlation between the development of the multiple organ dysfunction syndrome (MODS) and the elevated mortality associated with sepsis. The mechanisms responsible for MODS development are being studied, however, the main efforts regarding MODS evaluation have focused on oxygen delivery optimization and on the modulation of the characteristic inflammatory cascade of sepsis, all with negative results. Recent studies have shown that there is development of tissue acidosis, even when there are normal oxygen conditions and limited presence of tissue cellular necrosis or apoptosis, which would indicate that cellular energetic dysfunction may be a central element in MODS pathogenesis. Mitochondrias are the main source of cellular energy, central regulators of cell death and the main source for reactive oxygen species. Several mechanisms contribute to mitochondrial dysfunction during sepsis, that is blockage of pyruvate entry into the Krebs cycle, oxidative phosphorylation substrate use in other enzymatic complexes, enzymatic complex inhibition and membrane damage mediated by oxidative stress, and reduction in mitochondrial content. Hypoxia-inducible factor-1alpha (HIF-1alpha) is a nuclear transcription factor with a central role in the regulation of cellular oxygen homeostasis. Its induction under hypoxic conditions is associated to the expression of hundreds of genes that coordinate the optimization of cellular oxygen delivery and the cellular energy metabolism. HIF-1alpha can also be stabilized under normoxic condition during inflammation and this activation seems to be associated with a prominent pro-inflammatory profile, with lymphocytes dysfunction, and to a reduction in cellular oxygen consumption. Further studies should establish a role for HIF-1alpha as a therapeutic target.

Item Type:	Journal Article (Further Contribution)
Division/Institute:	04 Faculty of Medicine > Department of Intensive Care, Emergency Medicine and Anaesthesiology (DINA) > Clinic of Intensive Care
UniBE Contributor:	Regueira, Tomas Emilio, Djafarzadeh, Siamak
ISSN:	0210-5691
Publisher:	IDEPSA, International de Ediciones y Publicaciones, S.A.
Language:	English
Submitter:	Factscience Import
Date Deposited:	04 Oct 2013 15:13
Last Modified:	05 Dec 2022 14:22
Publisher DOI:	10.1016/j.medin.2008.10.002
PubMed ID:	19912970
Web of Science ID:	000281192200004
URI:	https://boris.unibe.ch/id/eprint/32222 (FactScience: 197231)