Variability of Mitochondrial Respiration in Relation to Sepsis-Induced Multiple Organ Dysfunction

Abstract

Ample experimental evidence suggests that sepsis could interfere with any mitochondrial function; however, the true role of mitochondrial dysfunction in the pathogenesis of sepsis-induced multiple organ dysfunction is still a matter of controversy. This review is primarily focused on mitochondrial oxygen consumption in various animal models of sepsis in relation to human disease and potential sources of variability in experimental results documenting decrease, increase or no change in mitochondrial respiration in various organs and species. To date, at least three possible explanations of sepsis-associated dysfunction of the mitochondrial respiratory system and consequently impaired energy production have been suggested: 1. Mitochondrial dysfunction is secondary to tissue hypoxia. 2. Mitochondria are challenged by various toxins or mediators of inflammation that impair oxygen utilization (cytopathic hypoxia). 3. Compromised mitochondrial respiration could be an active measure of survival strategy resembling stunning or hibernation. To reveal the true role of mitochondria in sepsis, sources of variability of experimental results based on animal species, models of sepsis, organs studied, or analytical approaches should be identified and minimized by the use of appropriate experimental models resembling human sepsis, wider use of larger animal species in preclinical studies, more detailed mapping of interspecies differences and organ-specific features of oxygen utilization in addition to use of complex and standardized protocols evaluating mitochondrial respiration.

A Multivariate Metabolomics Method for Estimating Platelet Mitochondrial Oxygen Consumption Rates in Patients with Sepsis

“…Notably, the role of taurine in sepsis is unclear; but it is highly concentrated in platelets and reportedly reduces coagulation and increases during animal hibernation [27,28]. We find the latter observation interesting, because it may play a role in the sepsis hibernation hypothesis, which theorizes that downregulated mitochondrial respiration acts as a defensive strategy to prevent sepsis-induced cell death [29].…”

Fetal Inflammatory Response Syndrome and Cerebral Oxygenation During Immediate Postnatal Transition in Preterm Neonates

“…Reduced oxygen consumption during inflammation and sepsis can be explained by mitochondrial dysfunction with impaired energy production ( 21 ). There are three possible mechanism for this mitochondrial dysfunction: (i) dysfunction is secondary due to tissue hypoxia, (ii) impairment of oxygen utilization due to cytokines, and (iii) active mitochondrial measure of survival strategy resembling stunning or hibernation.…”

Association of Mitochondrial Respiratory Chain Enzymes with the Risk and Mortality of Sepsis Among Chinese Children

“…Currently, the biological implications of mitochondrial dysfunction in sepsis have been widely evaluated [8,21,22]. Mitochondria produce ATP by transferring electrons from substrates sequentially across four respiratory chain complexes (I to IV) and two mobile carriers (coenzyme Q and cytochrome C) to nal electron acceptors [23]. Mitochondrial dysfunction is deemed as a key cellular event involved in the pathogenesis of multi-organ failure in sepsis, and it is secondary to tissue hypoxia and involves various toxins or mediators of in ammation that impair oxygen utilization (cytopathic hypoxia) [23,24].…”

“…Mitochondria produce ATP by transferring electrons from substrates sequentially across four respiratory chain complexes (I to IV) and two mobile carriers (coenzyme Q and cytochrome C) to nal electron acceptors [23]. Mitochondrial dysfunction is deemed as a key cellular event involved in the pathogenesis of multi-organ failure in sepsis, and it is secondary to tissue hypoxia and involves various toxins or mediators of in ammation that impair oxygen utilization (cytopathic hypoxia) [23,24]. There is evidence that damaged mitochondria contribute to NACHT, LRR and PYD domains-containing protein 3 (NLRP3) in ammasome-related sepsis [21].…”