The DOI matches its Crossref record; 61 of the 61 references it cites were found in a registry or an index.
Psychological Stress and Mitochondria: A Conceptual Framework
Open accessAbstract
Background: The integration of biological, psychological, and social factors in medicine has benefited from increasingly precise stress response biomarkers. Mitochondria, a subcellular organelle with its own genome, produce the energy required for life and generate signals that enable stress adaptation. An emerging concept proposes that mitochondria sense, integrate, and transduce psychosocial and behavioral factors into cellular and molecular modifications. Mitochondrial signaling might in turn contribute to the biological embedding of psychological states. Methods: A narrative literature review was conducted to evaluate evidence supporting this model implicating mitochondria in the stress response, and its implementation in behavioral and psychosomatic medicine. Results: Chronically, psychological stress induces metabolic and neuroendocrine mediators that cause structural and functional recalibrations of mitochondria, which constitutes mitochondrial allostatic load. Clinically, primary mitochondrial defects affect the brain, the endocrine system, and the immune systems that play a role in psychosomatic processes, suggesting a shared underlying mechanistic basis. Mitochondrial function and dysfunction also contribute to systemic physiological regulation through the release of mitokines and other metabolites. At the cellular level, mitochondrial signaling influences gene expression and epigenetic modifications, and modulates the rate of cellular aging. Conclusions: This evidence suggests that mitochondrial allostatic load represents a potential subcellular mechanism for transducing psychosocial experiences and the resulting emotional responses—both adverse and positive—into clinically meaningful biological and physiological changes. The associated article in this issue of Psychosomatic Medicine presents a systematic review of the effects of psychological stress on mitochondria. Integrating mitochondria into biobehavioral and psychosomatic research opens new possibilities to investigate how psychosocial factors influence human health and well-being across the life-span.
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Citations
Cites
Stress, social support, and the buffering hypothesis
Cohen, S., & Wills, T. A. (1985) · Psychological Bulletin · doi:10.1037/0033-2909.98.2.310 · Cited by 18,093
The Need for a New Medical Model: A Challenge for Biomedicine
Engel, G. L. (1977) · Science · doi:10.1126/science.847460 · Cited by 12,887
DNA methylation age of human tissues and cell types
Horvath, S. (2013) · Genome Biology · doi:10.1186/gb-2013-14-10-r115 · Cited by 7,075
Protective and Damaging Effects of Stress Mediators
McEwen, B. S. (1998) · New England Journal of Medicine · doi:10.1056/nejm199801153380307 · Cited by 6,733 · cited 1×
“The concepts of allostasis and allostatic load and overload emphasize that the same systems that help the body and brain adapt to experiences also contribute to pathophysiology when the same mediators are overused or dysregulated among themselves (50).”
BackgroundSelf-citationEffects of stress throughout the lifespan on the brain, behaviour and cognition
Lupien, S. J., McEwen, B. S., Gunnar, M. R., & Heim, C. (2009) · Nature Reviews Neuroscience · doi:10.1038/nrn2639 · Cited by 6,256
Self-citationPhysiology and neurobiology of stress and adaptation: central role of the brain
McEwen, B. S. (2007) · Physiological Reviews · doi:10.1152/physrev.00041.2006 · Cited by 5,429 · cited 2×
“These are adaptive in the face of danger as they increase vigilance, but at the cost of some cognitive acuity (82).”
BackgroundSelf-citationCirculating mitochondrial DAMPs cause inflammatory responses to injury
Zhang, Q., Raoof, M., Chen, Y., Sumi, Y., Sursal, T., Junger, W., Brohi, K., Itagaki, K., & Hauser, C. J. (2010) · Nature · doi:10.1038/nature08780 · Cited by 3,812
Nakahira, K., Haspel, J. A., Rathinam, V. A. K., Lee, S.-J., Dolinay, T., Lam, H. C., Englert, J. A., Rabinovitch, M., Cernadas, M., Kim, H. P., et al. (2011) · Nature Immunology · doi:10.1038/ni.1980 · Cited by 3,049
Accelerated telomere shortening in response to life stress
Epel, E. S., Blackburn, E. H., Lin, J., Dhabhar, F. S., Adler, N. E., Morrow, J. D., & Cawthon, R. M. (2004) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0407162101 · Cited by 3,002
Geroscience: Linking Aging to Chronic Disease
Kennedy, B. K., Berger, S. L., Brunet, A., Campisi, J., Cuervo, A. M., Epel, E. S., Franceschi, C., Lithgow, G. J., Morimoto, R. I., Pessin, J. E., et al. (2014) · Cell · doi:10.1016/j.cell.2014.10.039 · Cited by 2,764
Premature ageing in mice expressing defective mitochondrial DNA polymerase
Trifunovic, A., Wredenberg, A., Falkenberg, M., Spelbrink, J. N., Rovio, A. T., Bruder, C. E., Bohlooly-Y, M., Gidlöf, S., Oldfors, A., Wibom, R., et al. (2004) · Nature · doi:10.1038/nature02517 · Cited by 2,734
Mitochondrial DNA mutation associated with Leber’s hereditary optic neuropathy
Wallace, D. C., Singh, G., Lott, M. T., Hodge, J. A., Schurr, T. G., Lezza, A. M. S., Elsas, L. J., & Nikoskelainen, E. K. (1988) · Science · doi:10.1126/science.3201231 · Cited by 2,440
Oxidized mitochondrial DNA activates the NLRP3 inflammasome during apoptosis
Shimada, K., Crother, T. R., Karlin, J., Dagvadorj, J., Chiba, N., Chen, S., Ramanujan, V. K., Wolf, A. J., Vergnes, L., Ojcius, D. M., et al. (2012) · Immunity · doi:10.1016/j.immuni.2012.01.009 · Cited by 2,282
Mitochondrial DNA mutations, oxidative stress, and apoptosis in mammalian aging
Kujoth, G. C., Hiona, A., Pugh, T. D., Someya, S., Panzer, K., Wohlgemuth, S. E., Hofer, T., Seo, A. Y., Sullivan, R., Jobling, W. A., et al. (2005) · Science · doi:10.1126/science.1112125 · Cited by 2,165
Mitochondrial DNA stress primes the antiviral innate immune response
West, A. P., Khoury-Hanold, W., Staron, M., Tal, M. C., Pineda, C. M., Lang, S. M., Bestwick, M., Duguay, B. A., Raimundo, N., MacDuff, D. A., et al. (2015) · Nature · doi:10.1038/nature14156 · Cited by 1,975
Metabolic Pathways in Immune Cell Activation and Quiescence
Pearce, E. L., & Pearce, E. J. (2013) · Immunity · doi:10.1016/j.immuni.2013.04.005 · Cited by 1,692
Tlr signalling augments macrophage bactericidal activity through mitochondrial ros
West, A. P., Brodsky, I. E., Rahner, C., Woo, D. K., Erdjument-Bromage, H., Tempst, P., Walsh, M. C., Choi, Y., Shadel, G. S., & Ghosh, S. (2011) · Nature · doi:10.1038/nature09973 · Cited by 1,659
Chronic stress, glucocorticoid receptor resistance, inflammation, and disease risk
Cohen, S., Janicki-Deverts, D., Doyle, W. J., Miller, G. E., Frank, E., Rabin, B. S., & Turner, R. B. (2012) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1118355109 · Cited by 1,419
Mitochondria in innate immune responses
West, A. P., Shadel, G. S., & Ghosh, S. (2011) · Nature Reviews Immunology · doi:10.1038/nri2975 · Cited by 1,376
Seeman, T. E. (1997) · Archives of Internal Medicine · doi:10.1001/archinte.1997.00440400111013 · Cited by 1,368
Fueling Immunity: Insights into Metabolism and Lymphocyte Function
Pearce, E. L., Poffenberger, M. C., Chang, C.-H., & Jones, R. G. (2013) · Science · doi:10.1126/science.1242454 · Cited by 1,363
Mitochondrial Dynamics in the Regulation of Nutrient Utilization and Energy Expenditure
Liesa, M., & Shirihai, O. S. (2013) · Cell Metabolism · doi:10.1016/j.cmet.2013.03.002 · Cited by 1,341
Stress and cardiovascular disease
Steptoe, A., & Kivimäki, M. (2012) · Nature Reviews Cardiology · doi:10.1038/nrcardio.2012.45 · Cited by 1,321
Telomere dysfunction induces metabolic and mitochondrial compromise
Sahin, E., Colla, S., Liesa, M., Moslehi, J., Müller, F. L., Guo, M., Cooper, M., Kotton, D., Fabian, A. J., Walkey, C., et al. (2011) · Nature · doi:10.1038/nature09787 · Cited by 1,319 · cited 1×
“effectively decreases mitochondrial content and function, involving the down-regulation of peroxisome proliferator–activated receptorγ coactivator 1α signaling and mitochondrial biogenesis (160).”
The energetics of genome complexity.
Lane, N., & Martin, W. (2010) · Nature · doi:10.1038/nature09486 · Cited by 1,289
Mitochondrial DNA that escapes from autophagy causes inflammation and heart failure
Oka, T., Hikoso, S., Yamaguchi, O., Taneike, M., Takeda, T., Tamai, T., Oyabu, J., Murakawa, T., Nakayama, H., Nishida, K., et al. (2012) · Nature · doi:10.1038/nature10992 · Cited by 1,201
Brain on stress: how the social environment gets under the skin
McEwen, B. S. (2012) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1121254109 · Cited by 1,200
Self-citationStress- and Allostasis-Induced Brain Plasticity
McEwen, B. S., & Gianaros, P. J. (2011) · Annual Review of Medicine · doi:10.1146/annurev-med-052209-100430 · Cited by 1,171
Self-citationMitonuclear protein imbalance as a conserved longevity mechanism
Houtkooper, R. H., Mouchiroud, L., Ryu, D., Moullan, N., Katsyuba, E., Knott, G., Williams, R. W., & Auwerx, J. (2013) · Nature · doi:10.1038/nature12188 · Cited by 1,035
Reciprocal regulation of the neural and innate immune systems
Irwin, M. R., & Cole, S. W. (2011) · Nature Reviews Immunology · doi:10.1038/nri3042 · Cited by 910
Mitochondrial DNA deletions in human brain: regional variability and increase with advanced age
Corral-Debrinski, M., Horton, T., Lott, M. T., Shoffner, J. M., Flint Beal, M., & Wallace, D. C. (1992) · Nature Genetics · doi:10.1038/ng1292-324 · Cited by 890
McLaughlin, K. A., Conron, K. J., Koenen, K. C., & Gilman, S. E. (2010) · Psychological Medicine · doi:10.1017/s0033291709992121 · Cited by 855
Chronic inflammation induces telomere dysfunction and accelerates ageing in mice
Jurk, D., Wilson, C., Passos, J. F., Oakley, F., Correia-Melo, C., Greaves, L., Saretzki, G., Fox, C., Lawless, C., Anderson, R., et al. (2014) · Nature Communications · doi:10.1038/ncomms5172 · Cited by 819
Mitochondrial dysfunction accounts for the stochastic heterogeneity in telomere-dependent senescence
Passos, J. F., Saretzki, G., Ahmed, S., Nelson, G., Richter, T., Peters, H., Wappler, I., Birket, M. J., Harold, G., Schaeuble, K., et al. (2007) · PLoS Biology · doi:10.1371/journal.pbio.0050110 · Cited by 796 · cited 1×
“Mitochondrial ROS can cause telomere instability and shortening in vitro (157), and preliminary evidence suggests that individuals with mtDNA mutations”
BackgroundMitochondria are required for pro-ageing features of the senescent phenotype
Correia‐Melo, C., Marques, F. D., Anderson, R., Hewitt, G., Hewitt, R., Cole, J., Carroll, B. M., Miwa, S., Birch, J., Merz, A., et al. (2016) · The EMBO Journal · doi:10.15252/embj.201592862 · Cited by 796
Miller, G. E., Cohen, S., & Ritchey, A. K. (2002) · Health Psychology · doi:10.1037/0278-6133.21.6.531 · Cited by 769
Essex, M. J., Klein, M. H., Cho, E., & Kalin, N. H. (2002) · Biological Psychiatry · doi:10.1016/s0006-3223(02)01553-6 · Cited by 698
Endurance Exercise as a Countermeasure for Aging
Lanza, I. R., Short, D. K., Short, K. R., Raghavakaimal, S., Basu, R., Joyner, M. J., McConnell, J. P., & Nair, K. S. (2008) · Diabetes · doi:10.2337/db08-0349 · Cited by 582
The Emerging Field of Human Social Genomics
Slavich, G. M., & Cole, S. W. (2013) · Clinical Psychological Science · doi:10.1177/2167702613478594 · Cited by 523
Nakahira, K., Kyung, S.-Y., Rogers, A. J., Gazourian, L., Youn, S., Massaro, A. F., Quintana, C., Osorio, J. C., Wang, Z., Zhao, Y., et al. (2013) · PLoS Medicine · doi:10.1371/journal.pmed.1001577 · Cited by 445
A cannabinoid link between mitochondria and memory
Hebert-Chatelain, E., Desprez, T., Serrat, R., Bellocchio, L., Soria-Gomez, E., Busquets-Garcia, A., Pagano Zottola, A. C., Delamarre, A., Cannich, A., Vincent, P., et al. (2016) · Nature · doi:10.1038/nature20127 · Cited by 434
McManus, M. J., Murphy, M. P., & Franklin, J. L. (2011) · The Journal of Neuroscience · doi:10.1523/jneurosci.0552-11.2011 · Cited by 432
Frequency of hippocampal formation atrophy in normal aging and Alzheimer's disease
De Leon, M. J., George, A. E., Golomb, J., Tarshish, C., Convit, A., Kluger, A., De Santi, S., Mc Rae, T., Ferris, S. H., Reisberg, B., et al. (1997) · Neurobiology of Aging · doi:10.1016/s0197-4580(96)00213-8 · Cited by 429
Pinti, M., Cevenini, E., Nasi, M., De Biasi, S., Salvioli, S., Monti, D., Benatti, S., Gibellini, L., Cotichini, R., Stazi, M. A., et al. (2014) · European Journal of Immunology · doi:10.1002/eji.201343921 · Cited by 409
Rethinking inflammation: neural circuits in the regulation of immunity
Olofsson, P. S., Rosas‐Ballina, M., Levine, Y. A., & Tracey, K. J. (2012) · Immunological Reviews · doi:10.1111/j.1600-065x.2012.01138.x · Cited by 393 · cited 1×
“Immune cells are also a major source of inflammatory mediators (108), which feedback onto the brain and autonomic nervous system, and vice versa (109,110).”
BackgroundRapid regulation of steroidogenesis by mitochondrial protein import
Bose, H. S., Lingappa, V. R., & Miller, W. L. (2002) · Nature · doi:10.1038/417087a · Cited by 357
Interleukin-6 Covaries Inversely with Hippocampal Grey Matter Volume in Middle-Aged Adults
Marsland, A. L., Gianaros, P. J., Abramowitch, S. M., Manuck, S. B., & Hariri, A. R. (2008) · Biological Psychiatry · doi:10.1016/j.biopsych.2008.04.016 · Cited by 348
A mitochondrial bioenergetic etiology of disease
Wallace, D. C. (2013) · Journal of Clinical Investigation · doi:10.1172/jci61398 · Cited by 342
The power of exercise: buffering the effect of chronic stress on telomere length
Puterman, E., Lin, J., Blackburn, E., O'Donovan, A., Adler, N., & Epel, E. (2010) · PLoS ONE · doi:10.1371/journal.pone.0010837 · Cited by 339
Prospective reports of chronic life stress predict decreased grey matter volume in the hippocampus
Gianaros, P. J., Jennings, J. R., Sheu, L. K., Greer, P. J., Kuller, L. H., & Matthews, K. A. (2007) · NeuroImage · doi:10.1016/j.neuroimage.2006.10.045 · Cited by 324
Germline mitochondrial DNA mutations aggravate ageing and can impair brain development
Ross, J. M., Stewart, J. B., Hagström, E., Brené, S., Mourier, A., Coppotelli, G., Freyer, C., Lagouge, M., Hoffer, B. J., Olson, L., et al. (2013) · Nature · doi:10.1038/nature12474 · Cited by 273
Popov, V. I., & Bocharova, L. S. (1992) · Neuroscience · doi:10.1016/0306-4522(92)90337-2 · Cited by 203
SIRT3 regulates mitochondrial protein acetylation and intermediary metabolism
Hirschey, M. D., Shimazu, T., Huang, J. Y., Schwer, B., & Verdin, E. (2011) · Cold Spring Harbor Symposia on Quantitative Biology · doi:10.1101/sqb.2011.76.010850 · Cited by 180
Mitohormesis in exercise training
Merry, T. L., & Ristow, M. (2016) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2015.11.032 · Cited by 176
Puterman, E., Gemmill, A., Karasek, D., Weir, D., Adler, N. E., Prather, A. A., & Epel, E. S. (2016) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1525602113 · Cited by 165
Vincent, A. E., Turnbull, D. M., Eisner, V., Hajnóczky, G., & Picard, M. (2017) · Trends in Cell Biology · doi:10.1016/j.tcb.2017.08.009 · Cited by 135
Self-citationTyrka, A. R., Carpenter, L. L., Kao, H.-T., Porton, B., Philip, N. S., Ridout, S. J., Ridout, K. K., & Price, L. H. (2015) · Experimental Gerontology · doi:10.1016/j.exger.2015.04.002 · Cited by 125 · cited 1×
“56) (161,162), with the strength of the association being stronger in those having adverse childhood experiences and with a history of psychopathology (162).”
BackgroundAdrenal Mitochondria and Steroidogenesis: From Individual Proteins to Functional Protein Assemblies
Midzak, A., & Papadopoulos, V. (2016) · Frontiers in Endocrinology · doi:10.3389/fendo.2016.00106 · Cited by 114 · cited 1×
“that is regulated by and occurs in mitochondria (33,34), further”
BackgroundPuterman, E., & Epel, E. (2012) · Social and Personality Psychology Compass · doi:10.1111/j.1751-9004.2012.00465.x · Cited by 106
Mosconi, L., de Leon, M., Murray, J., E, L., Lu, J., Javier, E., McHugh, P., & Swerdlow, R. H. (2011) · Journal of Alzheimer s Disease · doi:10.3233/jad-2011-110866 · Cited by 97
Pieters, N., Janssen, B. G., Valeri, L., Cox, B., Cuypers, A., Dewitte, H., Plusquin, M., Smeets, K., & Nawrot, T. S. (2015) · Mechanisms of Ageing and Development · doi:10.1016/j.mad.2015.02.003 · Cited by 43
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Metadata
- Authors
- Picard, M., & McEwen, B. S.
- Venue
- Psychosomatic Medicine
- Published
- 2018-02
- Volume
- 80
- Issue
- 2
- Pages
- 126-140
- ISSN
- 0033-3174 (ISSN-L)
- 1534-7796
- OpenAlex
- W2791325895
- Cited by
- 307
- References
- 61
- FWCI
- 5.73
- Type
- journal article
- Language
- en
- Open access
- hybrid
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