MITOCHONDRIAL DYSFUNCTION AND MOLECULAR BIOMARKERS IN SEPSIS-INDUCED ACUTE RESPIRATORY DISTRESS SYNDROME: GENETIC AND METABOLIC MECHANISMS

Abstract

Background: Sepsis-induced acute respiratory distress syndrome (ARDS) remains a leading cause of mortality in intensive care units due to the progression of multiple organ dysfunction. Mitochondrial dysfunction has emerged as a central mechanism contributing to the pathogenesis of critical illness, including impaired oxidative phosphorylation, excessive production of reactive oxygen species, and mitochondrial DNA damage, all of which lead to cellular energy failure and dysregulated systemic inflammation.

Objective: This study aimed to summarize current knowledge on mitochondrial dysfunction in sepsis and ARDS, and to evaluate the diagnostic and prognostic value of emerging mitochondria-associated molecular biomarkers, as well as their potential clinical applications in anesthesiology and critical care.

Materials and Methods: A comprehensive literature review was conducted using national and international databases. A total of 65 relevant publications were included, encompassing clinical, experimental, and molecular-genetic studies focused on mitochondrial pathophysiology, biomarkers of mitochondrial injury, and metabolic therapeutic approaches. Additionally, studies utilizing bioinformatics, machine learning, and single-cell transcriptomic analyses were analyzed. Results: The analysis demonstrated that mitochondrial dysfunction represents an independent driver of multiple organ failure. Several candidate biomarkers, including ARID4B, RGS2, and TGM2, were identified as indicators of mitochondrial dysregulation in sepsis-induced ARDS. Mitochondrial alterations were strongly associated with immune imbalance and disease severity. Furthermore, biomarkers such as lactate, circulating mitochondrial DNA, cytochrome c, and oxidative stress markers showed potential for integration into risk stratification models.

Conclusion: Mitochondrial dysfunction plays a key pathogenic role in critical illness and represents a promising therapeutic target. Incorporation of mitochondria-related molecular biomarkers into clinical algorithms may improve prognostic accuracy, guide therapeutic decision-making, and enhance the effectiveness of personalized intensive care strategies in patients with severe sepsis and ARDS.