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Ribonucleotide synthesis by NME6 fuels mitochondrial gene expression

ABSTRACT: Replication and expression of the mitochondrial genome depend on the sufficient supply ofnucleotide building blocks to mitochondria. Dysregulated nucleotide metabolism is detrimental tomitochondrial genomes and can destabilise mitochondrial DNA and trigger inflammation. Here, wereport that a mitochondrial nucleoside diphosphate kinase, NME6, supplies mitochondria withpyrimidine ribonucleotides to drive the transcription of mitochondrial genes. Perturbation of NME6leads to the depletion of mitochondrial transcripts, destabilisation of the electron transport chainand impaired oxidative phosphorylation. These deficiencies are rescued upon supplementation withpyrimidine ribonucleosides. Moreover, NME6 is required for the maintenance of mitochondrial DNAwhen the access to cytosolic pyrimidine deoxyribonucleotides is limited. Our results, therefore, shedlight on the importance of mitochondrial ribonucleotide salvage for the synthesis of RNA andmitochondrial gene expression.The repository contains two internal projects which are identified by the internal IDs: 0187 and 0196. The raw files are indicated by the internal ID, and each Supplementary Table contains a reference to the internal ID. The project with the ID 0187 contains whole cell (WC) and immunoprecipitation (IP) data. Please see the file: SampleNamesForProjects.xlsx for more details.

INSTRUMENT(S): Orbitrap Exploris 480

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Cell Culture

SUBMITTER: Hendrik Nolte

LAB HEAD: Thomas Langer

PROVIDER: PXD038391 | Pride | 2023-05-04

REPOSITORIES: Pride

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