Bone marrow-derived mitochondrial DNA has limited capacity for inter-tissue transfer in vivo.

Autor: Tarnopolsky MA; Department of Pediatrics, McMaster University, Hamilton, ON, Canada., Kerkhof J; Molecular Genetics Laboratory, Molecular Diagnostics Division, London Health Sciences Centre, Children's Health Research Institute, London, ON, Canada., Stuart A; Molecular Genetics Laboratory, Molecular Diagnostics Division, London Health Sciences Centre, Children's Health Research Institute, London, ON, Canada., Bujak A; Exerkine Corporation, McMaster University, Hamilton, ON, Canada., Nilsson MI; Department of Pediatrics, McMaster University, Hamilton, ON, Canada., Hettinga B; Exerkine Corporation, McMaster University, Hamilton, ON, Canada., May L; Department of Pediatrics, McMaster University, Hamilton, ON, Canada., Rupar CA; Departments of Pathology and Laboratory Medicine, Pediatrics, Biochemistry and Children's Health Research Institute, Western University, London, ON, Canada., Sadikovic B; Molecular Genetics Laboratory, Molecular Diagnostics Division, London Health Sciences Centre, Children's Health Research Institute, London, ON, Canada.
Jazyk: angličtina
Zdroj: FASEB journal : official publication of the Federation of American Societies for Experimental Biology [FASEB J] 2020 Jul; Vol. 34 (7), pp. 9297-9306. Date of Electronic Publication: 2020 May 22.
DOI: 10.1096/fj.202000463R
Abstrakt: Studies have shown that mitochondrial DNA (mtDNA) can be exchanged between tissues; however, the mechanism(s) behind this phenomenon remain unclear. Exosomes and other extracellular vesicles (EVs) including microvesicles (MV) have been shown to contain mtDNA. EVs can be derived from a number of tissues; however, the source and relative proportion of EVs containing mtDNA remains unknown. We sampled whole blood and the EV fractions (exosome-enriched, MV-enriched, and apoptotic body-enriched) as well as several tissues (epithelial-cheek and urine sediment), connective (fibroblasts), and skeletal muscle in two subjects who received allogenic bone marrow transplants. Next generation sequencing of the mtDNA confirmed that all EV fractions contained mtDNA and most was derived from the donor, confirming that most of the EV fractions in the serum are bone marrow/blood cell-derived. Even after exposure to the donor mtDNA in EV fractions (and potentially free in the plasma) for years, there was little to no transfer of the donor mtDNA to the host mtDNA fraction in epithelial, connective, or skeletal muscle tissues. These data call into question the potential therapeutic use of bone marrow transplant or EV-based delivery systems for mtDNA-based disorders and establish bone marrow as the primary source of most of the mtDNA enriched EVs in serum.
(© 2020 Federation of American Societies for Experimental Biology.)
Databáze: MEDLINE
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