Acute psychological stress increases serum circulating cell-free mitochondrial DNA
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Abstract
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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Assessing presence of extracellular mitochondria or their fragments by measuring ccf-mtDNA levels could allow on-flight direct estimation of cellular stress to take preventive measures of cumulative damage.
“Assessing the presence of extracellular mitochondria or their fragments by measuring ccf-mtDNA levels could allow on-flight direct estimation of cellular stress to take preventive measures of cumulative damage196,199–206.”
From Key points for the development of antioxidant cocktails to prevent cellular stress and damage caused by reactive oxygen species (ROS) during manned space missions (2021) · cites this paper as [205]
The Discussion (page unavailable) describes serum ccf-mtDNA as a dynamic marker that rises rapidly after acute psychological stress, supporting its potential use in assessing a stress response. It does not establish that ccf-mtDNA directly measures cellular stress during flight or that monitoring it enables preventive measures against cumulative damage. (LLM, conf=0.86)
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- Authors
- Trumpff, C., Marsland, A. L., Basualto-Alarcón, C., Martin, J. L., Carroll, J. E., Sturm, G., Vincent, A. E., Mosharov, E. V., Gu, Z., Kaufman, B. A., & Picard, M.
- Affiliations
- Columbia University Irving Medical Center (US)
- University of Pittsburgh (US)
- Universidad de Aysén (CL)
- University of California, Los Angeles (US)
- Cornell University (US)
- Corresponding author
- Marsland, Anna L.
- Kaufman, Brett A.
- Picard, Martin
- ORCID
- Venue
- Psychoneuroendocrinology
- Publisher
- Elsevier BV
- Published
- 2019-08
- Volume
- 106
- Pages
- 268-276
- ISSN
- 0306-4530 (ISSN-L)
- PMC
- PMC6589121
- OpenAlex
- W2926182860
- Cited by
- 147
- References
- 11
- Citations by year
- 2026: 13 · 2025: 15 · 2024: 20 · 2023: 20 · 2022: 36 · 2021: 23 · 2020: 13 · 2019: 6 · 2014: 1
- FWCI
- 3.74
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Psychoneuroendocrinology (acceptedVersion)
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Universidad de Chile (submittedVersion, cc-by-nc-nd)
- Newcastle University ePrints (Newcastle Univesity)
- Funders
- NIH (NR08237, GM110424, GM119793, MH113011)
- Wharton Fund
- FONDECYT (3150623)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Extracellular vesicles in disease
- Keywords
- acute psychological stress, circulating cell-free mitochondrial DNA, cell-free DNA, mitochondria, glucocorticoid signaling, neuroendocrine stress response, middle-aged adults
- MeSH terms
- Cell-Free Nucleic Acids, Adult, DNA, Mitochondrial, Female, Humans, Male, Middle Aged, Mitochondria, Stress, Psychological
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