Max Planck Institute for Biology of Ageing, Cologne, Germany.
The CRUK Beatson Institute, Glasgow, UK.
EMBO J. 2023 Sep 18;42(18):e113256. doi: 10.15252/embj.2022113256. Epub 2023 Jul 13.
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.
线粒体基因组的复制和其所编码基因的表达都依赖于线粒体中有足够的核苷酸供应。因此，核苷酸代谢失调不仅会使线粒体基因组不稳定，还会影响其转录。在这里，我们报告说，一种线粒体核苷二磷酸激酶，NME6，为线粒体提供嘧啶核糖核苷酸，这些核苷酸对于线粒体基因的转录是必需的。NME6 功能的丧失导致线粒体转录本的消耗，以及电子传递链的不稳定和氧化磷酸化受损。这些缺陷可以通过嘧啶核糖核苷酸的外源供应来挽救。此外，当胞质嘧啶脱氧核苷酸的获取受到限制时，NME6 对于维持线粒体 DNA 也是必需的。因此，我们的结果揭示了核苷酸回收在线粒体基因表达中的重要作用。
