Serum cell-free mitochondrial DNA under a highly standardized and controlled stress induction

Cell-free mitochondrial DNA (ccf-mtDNA) is increasingly recognized as a biomarker of stress-related mitochondrial dysfunction. Acute psychological stress may induce ccf-mtDNA release, underscoring its potential role in stress physiology and adaptation. To further investigate this relationship, the present study examined acute stress-induced ccf-mtDNA dynamics in a controlled experimental setting. Twenty-seven healthy males (mean age: 23.78 ± 3.90 years) underwent both the Trier Social Stress Test (psychological stressor) and a resting condition. The kinetics of serum cell-free mitochondrial DNA (ccf-mtDNA) and serum cortisol were measured before and at 8 time points up to 105 min after the two stress conditions. After the TSST, ccf-mtDNA showed significant transient increases at +20 and +75 min, whereas cortisol exhibited the expected robust stress response. Our findings suggest that acute psychological stress can induce transient and heterogeneous changes in serum ccf-mtDNA, though these dynamics appear more modest and delayed than cortisol responses. Variability across studies underscores the need for standardized protocols and further research to clarify the mechanisms and moderators of ccf-mtDNA release under stress.