Background: Mitochondria play a crucial role in cellular processes such as energy metabolism, reactive oxygen species (ROS) generation, and apoptosis. Mitochondrial dysfunction induced by stress has been implicated in various health conditions. Circulating cell-free mitochondrial DNA (CFC-MT-DNA) has emerged as a potential biomarker reflecting mitochondrial damage under stress.
Methods: To evaluate the association between CFC-MT-DNA levels and human stress through a systematic review and meta-analysis of case-control studies. A comprehensive literature search was conducted across PubMed, Web of Science, and ScienceDirect databases up to September 2023. Eight eligible studies assessing CFC-MT-DNA levels in stressed versus control individuals were included. Data were analysed using RevMan 5.4 software.
Results: The meta-analysis revealed significantly elevated CFC-MT-DNA levels in individuals experiencing stress (P = 0.03), particularly in psychological stress-related conditions such as bipolar disorder and major depressive disorder. However, no significant increase was observed in physiological stress conditions, including diabetes and sports training. High heterogeneity (I2 = 96%) was observed across studies.
Conclusion: CFC-MT-DNA shows promise as a non-invasive biomarker for psychological stress. Further longitudinal and mechanistic studies are needed to clarify its role across different types of stress and its potential clinical utility.
Keywords: Biomarkers; CFC-MT-DNA; Copy number; Gene Ontology; Stress.