Evaluating Cell-Free Circulatory Mitochondrial DNA as a Comprehensive Biomarker for Stress: Meta-Analysis of Psychological and Physiological Stress Responses.

Publication date: Jun 21, 2025

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. 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. 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 (I = 96%) was observed across studies. 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.

Concepts Keywords
Biomarker Biomarkers
Bipolar CFC-MT-DNA
Diabetes Copy number
Free Gene Ontology
Mitochondrial Stress

Semantics

Type Source Name
disease MESH Physiological Stress Responses
pathway REACTOME Metabolism
pathway REACTOME Apoptosis
disease MESH Mitochondrial dysfunction
disease MESH psychological stress
disease MESH bipolar disorder
disease MESH major depressive disorder

Original Article

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