Ribonucleotide synthesis by NME6 fuels mitochondrial gene expression.

Autor: Grotehans N; Max Planck Institute for Biology of Ageing, Cologne, Germany., McGarry L; The CRUK Beatson Institute, Glasgow, UK., Nolte H; Max Planck Institute for Biology of Ageing, Cologne, Germany., Xavier V; The CRUK Beatson Institute, Glasgow, UK., Kroker M; Max Planck Institute for Biology of Ageing, Cologne, Germany., Narbona-Pérez ÁJ; Max Planck Institute for Biology of Ageing, Cologne, Germany., Deshwal S; Max Planck Institute for Biology of Ageing, Cologne, Germany., Giavalisco P; Max Planck Institute for Biology of Ageing, Cologne, Germany., Langer T; Max Planck Institute for Biology of Ageing, Cologne, Germany.; Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), University of Cologne, Cologne, Germany., MacVicar T; The CRUK Beatson Institute, Glasgow, UK.
Jazyk: angličtina
Zdroj: The EMBO journal [EMBO J] 2023 Sep 18; Vol. 42 (18), pp. e113256. Date of Electronic Publication: 2023 Jul 13.
DOI: 10.15252/embj.2022113256
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.
(© 2023 The Authors. Published under the terms of the CC BY 4.0 license.)
Databáze: MEDLINE
Externí odkaz: