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Stress and circulating cell-free mitochondrial DNA : A systematic review of human studies, physiological considerations, and technical recommendations

Trumpff, Caroline ; Michelson, Jeremy ; Lagranha, Claudia J. ; Taleon, Veronica ; Karan, Kalpita R. ; Sturm, Gabriel ; Lindqvist, Daniel LU ; Fernström, Johan LU ; Moser, Dirk and Kaufman, Brett A. , et al. (2021) In Mitochondrion 59. p.225-245
Abstract

Cell-free mitochondrial DNA (cf-mtDNA) is a marker of inflammatory disease and a predictor of mortality, but little is known about cf-mtDNA in relation to psychobiology. A systematic review of the literature reveals that blood cf-mtDNA varies in response to common real-world stressors including psychopathology, acute psychological stress, and exercise. Moreover, cf-mtDNA is inducible within minutes and exhibits high intra-individual day-to-day variation, highlighting the dynamic regulation of cf-mtDNA levels. We discuss current knowledge on the mechanisms of cf-mtDNA release, its forms of transport (“cell-free” does not mean “membrane-free”), potential physiological functions, putative cellular and neuroendocrine triggers, and factors... (More)

Cell-free mitochondrial DNA (cf-mtDNA) is a marker of inflammatory disease and a predictor of mortality, but little is known about cf-mtDNA in relation to psychobiology. A systematic review of the literature reveals that blood cf-mtDNA varies in response to common real-world stressors including psychopathology, acute psychological stress, and exercise. Moreover, cf-mtDNA is inducible within minutes and exhibits high intra-individual day-to-day variation, highlighting the dynamic regulation of cf-mtDNA levels. We discuss current knowledge on the mechanisms of cf-mtDNA release, its forms of transport (“cell-free” does not mean “membrane-free”), potential physiological functions, putative cellular and neuroendocrine triggers, and factors that may contribute to cf-mtDNA removal from the circulation. A review of in vitro, pre-clinical, and clinical studies shows conflicting results around the dogma that physiological forms of cf-mtDNA are pro-inflammatory, opening the possibility of other physiological functions, including the cell-to-cell transfer of whole mitochondria. Finally, to enhance the reproducibility and biological interpretation of human cf-mtDNA research, we propose guidelines for blood collection, cf-mtDNA isolation, quantification, and reporting standards, which can promote concerted advances by the community. Defining the mechanistic basis for cf-mtDNA signaling is an opportunity to elucidate the role of mitochondria in brain-body interactions and psychopathology.

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organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
cell-free DNA, Mitochondria, mtDNA, Non-inflammatory effects, Psychosocial stress, Standard protocol
in
Mitochondrion
volume
59
pages
21 pages
publisher
Elsevier
external identifiers
  • pmid:33839318
  • scopus:85108301236
ISSN
1567-7249
DOI
10.1016/j.mito.2021.04.002
language
English
LU publication?
yes
id
c152f547-39f7-49bf-9624-cd76391a2a9a
date added to LUP
2021-08-11 11:44:46
date last changed
2024-04-20 10:05:40
@article{c152f547-39f7-49bf-9624-cd76391a2a9a,
  abstract     = {{<p>Cell-free mitochondrial DNA (cf-mtDNA) is a marker of inflammatory disease and a predictor of mortality, but little is known about cf-mtDNA in relation to psychobiology. A systematic review of the literature reveals that blood cf-mtDNA varies in response to common real-world stressors including psychopathology, acute psychological stress, and exercise. Moreover, cf-mtDNA is inducible within minutes and exhibits high intra-individual day-to-day variation, highlighting the dynamic regulation of cf-mtDNA levels. We discuss current knowledge on the mechanisms of cf-mtDNA release, its forms of transport (“cell-free” does not mean “membrane-free”), potential physiological functions, putative cellular and neuroendocrine triggers, and factors that may contribute to cf-mtDNA removal from the circulation. A review of in vitro, pre-clinical, and clinical studies shows conflicting results around the dogma that physiological forms of cf-mtDNA are pro-inflammatory, opening the possibility of other physiological functions, including the cell-to-cell transfer of whole mitochondria. Finally, to enhance the reproducibility and biological interpretation of human cf-mtDNA research, we propose guidelines for blood collection, cf-mtDNA isolation, quantification, and reporting standards, which can promote concerted advances by the community. Defining the mechanistic basis for cf-mtDNA signaling is an opportunity to elucidate the role of mitochondria in brain-body interactions and psychopathology.</p>}},
  author       = {{Trumpff, Caroline and Michelson, Jeremy and Lagranha, Claudia J. and Taleon, Veronica and Karan, Kalpita R. and Sturm, Gabriel and Lindqvist, Daniel and Fernström, Johan and Moser, Dirk and Kaufman, Brett A. and Picard, Martin}},
  issn         = {{1567-7249}},
  keywords     = {{cell-free DNA; Mitochondria; mtDNA; Non-inflammatory effects; Psychosocial stress; Standard protocol}},
  language     = {{eng}},
  pages        = {{225--245}},
  publisher    = {{Elsevier}},
  series       = {{Mitochondrion}},
  title        = {{Stress and circulating cell-free mitochondrial DNA : A systematic review of human studies, physiological considerations, and technical recommendations}},
  url          = {{http://dx.doi.org/10.1016/j.mito.2021.04.002}},
  doi          = {{10.1016/j.mito.2021.04.002}},
  volume       = {{59}},
  year         = {{2021}},
}