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Ribonucleotide synthesis by NME6 fuels mitochondrial gene expression.
EMBO J. 42:e113256 (2023)
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.
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Publication type
Article: Journal article
Document type
Scientific Article
Keywords
Nme6 ; Mitochondria ; Mitochondrial Dna ; Mitochondrial Transcription ; Nucleotide Metabolism
ISSN (print) / ISBN
0261-4189
e-ISSN
1460-2075
Journal
EMBO Journal, The
Quellenangaben
Volume: 42,
Issue: 18,
Article Number: e113256
Publisher
Wiley
Publishing Place
Heidelberg, Germany
Non-patent literature
Publications
Reviewing status
Peer reviewed
Institute(s)
Institute of Metabolism and Cell Death (MCD)