Psychoneuroendocrinology, Volume 106, August 2019, Pages 268-276
aDepartment of Psychiatry, Division of Behavioral Medicine, Columbia University Irving Medical Center, New York, NY, 10032, USA
bNew York State Psychiatric Institute, New York, NY, 10032, USA
cDepartment of Psychology, University of Pittsburgh, Pittsburgh, PA, 15260, USA
dUniversidad de Aysén, Coyhaique, Chile
eAnatomy and Legal Medicine Department, Faculty of Medicine, Universidad de Chile, Santiago, Chile
fDepartment of Medicine, Division of Cardiology, Vascular Medicine Institute, Center for Metabolism and Mitochondrial Medicine, University of Pittsburgh Medical School, Pittsburgh, PA, 15261, USA
gCousins Center for Psychoneuroimmunology, Semel Institute for Neuroscience and Human Behavior, University of California, Los Angeles, CA, 90095, USA
hWellcome Trust Centre for Mitochondrial Research, Institute of Neurosciences, Newcastle University, Newcastle upon Tyne, NE2 4HH, UK
iDepartment of Neurology, H. Houston Merritt Center, Columbia Translational Neuroscience Initiative, Columbia University Irving Medical Center, New York, NY, 10032, USA
jDivision of Nutritional Sciences, Cornell University, Ithaca, New York, NY, 14850, USA
kColumbia Aging Center, Columbia University Mailman School of Public Health, New York, NY, 10032, USA
Received 30 November 2018, Revised 20 March 2019, Accepted 25 March 2019, Available online 28 March 2019.
•Ccf-mtDNA is a pro-inflammatory molecule elevated with aging and inflammatory diseases.
•Psychological stress rapidly and selectively increases serum ccf-mtDNA, not ccf-nDNA.
•The effect size for stress-induced elevation in serum ccf-mtDNA is larger in men.
Intrinsic biological mechanisms transduce psychological stress into physiological adaptation that requires energy, but the role of mitochondria and mitochondrial DNA (mtDNA) in this process has not been defined in humans. Here, we show that similar to physical injury, exposure to psychological stress increases serum circulating cell-free mtDNA (ccf-mtDNA) levels. Healthy midlife adults exposed on two separate occasions to a brief psychological challenge exhibited a 2-3-fold increase in ccf-mtDNA, with no change in ccf-nuclear DNA levels, establishing the magnitude and specificity for ccf-mtDNA reactivity. In cell-based studies, we show that glucocorticoid signaling – a consequence of psychological stress in humans – is sufficient to induce mtDNA extrusion in a time frame consistent with stress-induced ccf-mtDNA increase. Collectively, these findings provide evidence that acute psychological stress induces ccf-mtDNA and implicate neuroendocrine signaling as a potential trigger for ccf-mtDNA release. Further controlled work is needed to confirm that observed increases in ccf-mtDNA result from stress exposure and to determine the functional significance of this effect.