Acute psychological stress increases serum circulating cell-free mitochondrial DNA

Psychoneuroendocrinology, Volume 106, August 2019, Pages 268-276


Anna L.Marslandc


James L.Martinf

Judith E.Carrollg


Amy E.Vincentah

Eugene V.Mosharovabi


Brett A.Kaufmanf


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.



•Circulating cell-free mitochondrial DNA (ccf-mtDNA) is released from mitochondria.

•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.

•Neuroendocrine signaling triggers mtDNA extrusion in primary human fibroblasts.


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.

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About S. R. Zelenz 119 Articles
S.R. Zelenz has worked in education for 20 years. Working with students from all walks of life, cultures, races, and social diversity, Zelenz’s research in Educational Leadership led to finding a better way to approach learning for students with trauma histories. Many were juvenile offenders, gang members, diagnosed with varying behavioral disorders, or had family histories of violence, murder, or narcissistic parenting. This research could not be effectively accomplished without further understanding: how epigenetic trauma inheritance may be impacting these students; how brain development from trauma may be impacting their behavioral and emotional development; as well as deep understanding of psychology and its varying classifications for behavioral and personality disorders. The goal is to find solutions for changing the conversation and making a real difference for these students. She has also worked with nonprofits of varying focus areas for the last 25 years. Her undergraduate degree in Arts Administration and Music prepared her for managing nonprofits of any size as well as procuring funding so that they can achieve their goals. Pairing her nonprofit background with her education background, she has been able to make a difference for over 200 nonprofits worldwide, written curriculum for schools across the globe, and assisted many arts organizations through performance and management.