Ribonucleotide synthesis by NME6 fuels mitochondrial gene expression

Abstract

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.

SARS-Cov2 seasonality and adaptation are driven by solar activity.

“…Leading to the loss of components of the OXPHOS system, lowering mitochondrial respiration and the production of ATP. [80] Although previous mechanisms just try to explain a subset of the different symptoms experienced by long covid patients. They provide a series of possible targets for either treatment development or possible molecular markers.…”