Sepsis-induced mitochondrial dysfunction: A narrative review

Wagner Nedel; Caroline Deutschendorf; Luis Valmor Cruz Portela

doi:10.5492/wjccm.v12.i3.139

Sepsis-induced mitochondrial dysfunction: A narrative review

World J Crit Care Med. 2023 Jun 9;12(3):139-152. doi: 10.5492/wjccm.v12.i3.139.

Authors

Wagner Nedel^{1

2

3}, Caroline Deutschendorf⁴, Luis Valmor Cruz Portela²

Affiliations

¹ Intensive Care Unit, Grupo Hospitalar Conceição, Porto Alegre 91350200, Brazil.
² Laboratory of Neurotrauma and Biomarkers, Departamento de Bioquímica, ICBS, Universidade Federal do Rio Grande do Sul, Porto Alegre 90035-003, Brazil.
³ Brazilian Research in Intensive Care Network-BRICNet, São Paulo 04039-002, Brazil. wagnernedel@gmail.com.
⁴ Infection Control Committee, Hospital de Clínicas de Porto Alegre, Porto Alegre 90410-000, Brazil.

Abstract

Sepsis represents a deranged and exaggerated systemic inflammatory response to infection and is associated with vascular and metabolic abnormalities that trigger systemic organic dysfunction. Mitochondrial function has been shown to be severely impaired during the early phase of critical illness, with a reduction in biogenesis, increased generation of reactive oxygen species and a decrease in adenosine triphosphate synthesis of up to 50%. Mitochondrial dysfunction can be assessed using mitochondrial DNA concentration and respirometry assays, particularly in peripheral mononuclear cells. Isolation of monocytes and lymphocytes seems to be the most promising strategy for measuring mitochondrial activity in clinical settings because of the ease of collection, sample processing, and clinical relevance of the association between metabolic alterations and deficient immune responses in mononuclear cells. Studies have reported alterations in these variables in patients with sepsis compared with healthy controls and non-septic patients. However, few studies have explored the association between mitochondrial dysfunction in immune mononuclear cells and unfavorable clinical outcomes. An improvement in mitochondrial parameters in sepsis could theoretically serve as a biomarker of clinical recovery and response to oxygen and vasopressor therapies as well as reveal unexplored pathophysiological mechanistic targets. These features highlight the need for further studies on mitochondrial metabolism in immune cells as a feasible tool to evaluate patients in intensive care settings. The evaluation of mitochondrial metabolism is a promising tool for the evaluation and management of critically ill patients, especially those with sepsis. In this article, we explore the pathophysiological aspects, main methods of measurement, and the main studies in this field.

Keywords: Inflammation; Mitochondria; Mitochondrial dysfunction; Oxidative phosphorylation; Respirometry; Sepsis.

Publication types

Review