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Ribonucleotide synthesis by NME6 fuels mitochondrial gene expression.

The EMBO journal (2023-07-13)
Nils Grotehans, Lynn McGarry, Hendrik Nolte, Vanessa Xavier, Moritz Kroker, Álvaro Jesús Narbona-Pérez, Soni Deshwal, Patrick Giavalisco, Thomas Langer, Thomas MacVicar
ABSTRAKT

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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Sigma-Aldrich
Anti-NME6 antibody produced in rabbit, Prestige Antibodies® Powered by Atlas Antibodies, affinity isolated antibody, buffered aqueous glycerol solution
Sigma-Aldrich
DAPI, for nucleic acid staining
Sigma-Aldrich
Anti-DNA Antibody, clone AC-30-10, clone AC-30-10, Chemicon®, from mouse