Department of Medical Biochemistry and Biophysics, Umeå University, Umeå, Sweden.
EMBO J. 2023 Sep 18;42(18):e114990. doi: 10.15252/embj.2023114990. Epub 2023 Aug 7.
The building blocks for RNA and DNA are made in the cytosol, meaning mitochondria depend on the import and salvage of ribonucleoside triphosphates (rNTPs) and deoxyribonucleoside triphosphates (dNTPs) for the synthesis of their own genetic material. While extensive research has focused on mitochondrial dNTP homeostasis due to its defects being associated with various mitochondrial DNA (mtDNA) depletion and deletion syndromes, the investigation of mitochondrial rNTP homeostasis has received relatively little attention. In this issue of the EMBO Journal, Grotehans et al provide compelling evidence of a major role for NME6, a mitochondrial nucleoside diphosphate kinase, in the conversion of pyrimidine ribonucleoside diphosphates into the corresponding triphosphates. These data also suggest a significant physiological role for NME6, as its absence results in the depletion of mitochondrial transcripts and destabilization of the electron transport chain (Grotehans et al, 2023).
RNA 和 DNA 的构建模块在细胞质中合成，这意味着线粒体依赖于核苷酸三磷酸（rNTPs）和脱氧核苷酸三磷酸（dNTPs）的输入和回收来合成自身的遗传物质。由于线粒体 dNTP 稳态的缺陷与各种线粒体 DNA（mtDNA）耗竭和缺失综合征有关，因此大量研究集中在这一领域，而线粒体 rNTP 稳态的研究相对较少。在本期《欧洲分子生物学组织杂志》中，Grotehans 等人提供了令人信服的证据，证明线粒体核苷二磷酸激酶 NME6 在将嘧啶核糖核苷二磷酸转化为相应的三磷酸中起着重要作用。这些数据还表明 NME6 具有重要的生理作用，因为其缺失会导致线粒体转录物耗竭和电子传递链的不稳定（Grotehans 等人，2023 年）。
