Regulation of Mother-to-Offspring Transmission of mtDNA Heteroplasmy.
embryo
germline selection
heteroplasmy
mitochondria
mitochondrial replacement
mtDNA competition
mtDNA inheritance
Journal
Cell metabolism
ISSN: 1932-7420
Titre abrégé: Cell Metab
Pays: United States
ID NLM: 101233170
Informations de publication
Date de publication:
03 12 2019
03 12 2019
Historique:
received:
22
01
2019
revised:
12
06
2019
accepted:
10
09
2019
pubmed:
8
10
2019
medline:
22
9
2020
entrez:
8
10
2019
Statut:
ppublish
Résumé
mtDNA is present in multiple copies in each cell derived from the expansions of those in the oocyte. Heteroplasmy, more than one mtDNA variant, may be generated by mutagenesis, paternal mtDNA leakage, and novel medical technologies aiming to prevent inheritance of mtDNA-linked diseases. Heteroplasmy phenotypic impact remains poorly understood. Mouse studies led to contradictory models of random drift or haplotype selection for mother-to-offspring transmission of mtDNA heteroplasmy. Here, we show that mtDNA heteroplasmy affects embryo metabolism, cell fitness, and induced pluripotent stem cell (iPSC) generation. Thus, genetic and pharmacological interventions affecting oxidative phosphorylation (OXPHOS) modify competition among mtDNA haplotypes during oocyte development and/or at early embryonic stages. We show that heteroplasmy behavior can fall on a spectrum from random drift to strong selection, depending on mito-nuclear interactions and metabolic factors. Understanding heteroplasmy dynamics and its mechanisms provide novel knowledge of a fundamental biological process and enhance our ability to mitigate risks in clinical applications affecting mtDNA transmission.
Identifiants
pubmed: 31588014
pii: S1550-4131(19)30510-8
doi: 10.1016/j.cmet.2019.09.007
pmc: PMC6899444
pii:
doi:
Substances chimiques
DNA, Mitochondrial
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
1120-1130.e5Commentaires et corrections
Type : CommentIn
Informations de copyright
Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.
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