Department of Chemistry, Life Sciences and Environmental Sustainability, University of Parma, Parco Area delle Scienze 11/A, 43124 Parma, Italy.
Department of Medicine and Surgery, University of Parma, Via Gramsci 14, 43126 Parma, Italy.
Int J Mol Sci. 2023 Jan 22;24(3):2178. doi: 10.3390/ijms24032178.
In eukaryotes, mitochondrial RNAs (mt-tRNAs and mt-rRNAs) are subject to specific nucleotide modifications, which are critical for distinct functions linked to the synthesis of mitochondrial proteins encoded by mitochondrial genes, and thus for oxidative phosphorylation. In recent years, mutations in genes encoding for mt-RNAs modifying enzymes have been identified as being causative of primary mitochondrial diseases, which have been called modopathies. These latter pathologies can be caused by mutations in genes involved in the modification either of tRNAs or of rRNAs, resulting in the absence of/decrease in a specific nucleotide modification and thus on the impairment of the efficiency or the accuracy of the mitochondrial protein synthesis. Most of these mutations are sporadic or private, thus it is fundamental that their pathogenicity is confirmed through the use of a model system. This review will focus on the activity of genes that, when mutated, are associated with modopathies, on the molecular mechanisms through which the enzymes introduce the nucleotide modifications, on the pathological phenotypes associated with mutations in these genes and on the contribution of the yeast to confirming the pathogenicity of novel mutations and, in some cases, for defining the molecular defects.
在真核生物中，线粒体 RNA（mt-tRNA 和 mt-rRNA）受到特定核苷酸修饰的影响，这些修饰对于与线粒体基因编码的线粒体蛋白合成相关的不同功能至关重要，进而对于氧化磷酸化过程也是至关重要的。近年来，编码 mt-RNA 修饰酶的基因突变已被确定为原发性线粒体疾病的致病原因，这些疾病被称为 modopathies。这些疾病可能是由于参与 tRNA 或 rRNA 修饰的基因中的突变引起的，导致特定核苷酸修饰的缺失/减少，从而影响线粒体蛋白合成的效率或准确性。这些突变大多数是散发性的或特发性的，因此，通过使用模型系统来确认其致病性至关重要。这篇综述将重点介绍与 modopathies 相关的基因突变、酶引入核苷酸修饰的分子机制、这些基因中的突变与相关病理表型以及酵母在确认新突变的致病性以及在某些情况下定义分子缺陷方面的贡献。
