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Preferential amplification of a human mitochondrial DNA deletion in vitro and in vivo

Lookup NU author(s): Dr Oliver Russell, Pavandeep Rai, Dr Amy Reeve, Dr Karolina Rygiel, Professor Majlinda LakoORCiD, Professor Robert Taylor, Professor Robert Lightowlers, Emeritus Professor Doug Turnbull



This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).


© The Author(s) 2018. We generated induced pluripotent stem cells (iPSCs) from patient fibroblasts to yield cell lines containing varying degrees of heteroplasmy for a m.13514 A > G mtDNA point mutation (2 lines) and for a 6 kb single, large scale mtDNA deletion (3 lines). Long term culture of the iPSCs containing a single, large-scale mtDNA deletion showed consistent increase in mtDNA deletion levels with time. Higher levels of mtDNA heteroplasmy correlated with increased respiratory deficiency. To determine what changes occurred in deletion level during differentiation, teratomas comprising all three embryonic germ layers were generated from low (20%) and intermediate heteroplasmy (55%) mtDNA deletion clones. Regardless of whether iPSCs harbouring low or intermediate mtDNA heteroplasmy were used, the final levels of heteroplasmy in all teratoma germ layers increased to a similar high level (>60%). Thus, during human stem cell division, cells not only tolerate high mtDNA deletion loads but seem to preferentially replicate deleted mtDNA genomes. This has implications for the involvement of mtDNA deletions in both disease and ageing.

Publication metadata

Author(s): Russell OM, Fruh I, Rai PK, Marcellin D, Doll T, Reeve A, Germain M, Bastien J, Rygiel KA, Cerino R, Sailer AW, Lako M, Taylor RW, Mueller M, Lightowlers RN, Turnbull DM, Helliwell SB

Publication type: Article

Publication status: Published

Journal: Scientific Reports

Year: 2018

Volume: 8

Issue: 1

Online publication date: 29/01/2018

Acceptance date: 27/12/2017

Date deposited: 13/02/2018

ISSN (print): 2045-2322

Publisher: Nature Publishing Group


DOI: 10.1038/s41598-018-20064-2


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Funder referenceFunder name
Wellcome Trust