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Wiener Medizinische Wochenschrift

, Volume 160, Issue 5–6, pp 118–123 | Cite as

Mitochondrial function and dysfunction in sepsis

  • Martina Wendel
  • Axel R. Heller
Themenschwerpunkt

Summary

Mitochondria are the key source of cellular ATP and their structure and function are markedly affected by pathophysiologic processes associated with the host's response to invading pathogens. In particular, the highly reactive compound peroxynitrite, generated by the reaction of nitric oxide and superoxide anions, inhibits mitochondrial enzymes and damages lipids, proteins, and nucleic acids. Enhanced oxidative stress induces DNA strand breaks that are repaired by activation of poly(ADP-ribose)polymerase (PARP). This process consumes large amounts of nicotinamide adenine dinucleotide (NAD+) leading to cellular NAD+ depletion that impairs flux of reducing equivalents into the respiratory chain and also further promotes inflammation. In experimental studies, novel therapeutic strategies that aim to ameliorate the host's pathogen response or to modulate intracellular signaling events related to oxidative stress protected mitochondrial function and preserved cellular respiration ultimately leading to improved organ function.

Keywords

Sepsis Mitochondria Cytokines Reactive oxygen species Nitric oxide Reactive nitrogen species 

Mitochondriale Funktion und Dysfunktion bei der Sepsis

Zusammenfassung

Die Mitochondrien sind die quantitative bedeutsamste ATP-Quelle von Zellen. Durch die pathophysiologischen Vorgänge, die im Verlauf der Abwehr von eindringenden Miroorganismen in Gang gesetzt werden, kommt es zu einer Beeinrächtigung von Funktion und Struktur der Mitochondrien. Insbesondere das hochreaktive Peroxynitrit, das aus der Reaktion von Stickstoffmonoxid und Superoxid-Anionen entsteht, schädigt die mitochondrialen Lipide, Proteine und Nukleinsäuren. Der starke oxidative Stress induziert DNA-Strangbrüche, die unter Aktivierung der Poly(ADP-Ribose)-Polymerase repariert werden. Dieser Prozess verbraucht große Mengen an Nicotinamid-Dinucleotid (NAD+), wodurch es zur zellulären NAD+-Verarmung kommt. Dies beeinträchtigt die Einschleusung von Elektronen in die Atmungskette und verstärkt die Inflammation. Neue therapeutische Strategien, die auf eine Abschwächung der Wirtsreaktion auf eindringende Mikroorganismen oder auf eine Modulation intrazellulärer Signalkaskaden, die zu oxidativem Stress führen, abzielen, konnten in experimentellen Studien die mitochondriale Funktion und letztlich auch die Organfunktion verbessern.

Schlüsselwörter

Sepsis Mitochondrien Zytokine Reaktive Sauerstoffspezies Reaktive Stickstoffspezies 

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Copyright information

© Springer-Verlag 2010

Authors and Affiliations

  1. 1.Fachklinik Prinzregent LuitpoldScheideggGermany
  2. 2.Medical Faculty Carl-Gustav-Carus, Department of Anesthesiology and Critical Care MedicineUniversity of TechnologyDresdenGermany

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