Ribonucleotide synthesis by NME6 fuels mitochondrial gene expression.
NME6
mitochondria
mitochondrial DNA
mitochondrial transcription
nucleotide metabolism
Journal
The EMBO journal
ISSN: 1460-2075
Titre abrégé: EMBO J
Pays: England
ID NLM: 8208664
Informations de publication
Date de publication:
18 09 2023
18 09 2023
Historique:
revised:
07
06
2023
received:
11
12
2022
accepted:
19
06
2023
medline:
19
9
2023
pubmed:
13
7
2023
entrez:
13
7
2023
Statut:
ppublish
Résumé
Replication of the mitochondrial genome and expression of the genes it encodes both depend on a sufficient supply of nucleotides to mitochondria. Accordingly, dysregulated nucleotide metabolism not only destabilises the mitochondrial genome, but also affects its transcription. Here, we report that a mitochondrial nucleoside diphosphate kinase, NME6, supplies mitochondria with pyrimidine ribonucleotides that are necessary for the transcription of mitochondrial genes. Loss of NME6 function leads to the depletion of mitochondrial transcripts, as well as destabilisation of the electron transport chain and impaired oxidative phosphorylation. These deficiencies are rescued by an exogenous supply of pyrimidine ribonucleosides. Moreover, NME6 is required for the maintenance of mitochondrial DNA when the access to cytosolic pyrimidine deoxyribonucleotides is limited. Our results therefore reveal an important role for ribonucleotide salvage in mitochondrial gene expression.
Identifiants
pubmed: 37439264
doi: 10.15252/embj.2022113256
pmc: PMC10505918
doi:
Substances chimiques
Pyrimidines
0
Nucleotides
0
DNA, Mitochondrial
0
Ribonucleotides
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e113256Commentaires et corrections
Type : CommentIn
Informations de copyright
© 2023 The Authors. Published under the terms of the CC BY 4.0 license.
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