Replication and expression of the mitochondrial genome depend on the sufficient supply of nucleotide building blocks to mitochondria. Dysregulated nucleotide metabolism is detrimental to mitochondrial genomes and can destabilise mitochondrial DNA and trigger inflammation. Here, we report that a mitochondrial nucleoside diphosphate kinase, NME6, supplies mitochondria with pyrimidine ribonucleotides to drive the transcription of mitochondrial genes. Perturbation of NME6 leads to the depletion of mitochondrial transcripts, destabilisation of the electron transport chain and impaired oxidative phosphorylation. These deficiencies are rescued upon supplementation with pyrimidine ribonucleosides. Moreover, NME6 is required for the maintenance of mitochondrial DNA when the access to cytosolic pyrimidine deoxyribonucleotides is limited. Our results, therefore, shed light on the importance of mitochondrial ribonucleotide salvage for the synthesis of RNA and mitochondrial 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.