Intra-mitochondrial Methylation Deficiency Due to Mutations in SLC25A26.
Intra-mitochondrial Methylation Deficiency Due to Mutations in SLC25A26.
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SLC25A26 基因突变导致的线粒体内甲基化缺陷
DOI：
10.1016/j.ajhg.2015.09.013
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发表时间：
2015-11-05
影响因子：
9.8
通讯作者：
Wedell A
中科院分区：
文献类型：
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作者：
Kishita Y;Pajak A;Bolar NA;Marobbio CM;Maffezzini C;Miniero DV;Monné M;Kohda M;Stranneheim H;Murayama K;Naess K;Lesko N;Bruhn H;Mourier A;Wibom R;Nennesmo I;Jespers A;Govaert P;Ohtake A;Van Laer L;Loeys BL;Freyer C;Palmieri F;Wredenberg A;Okazaki Y;Wedell A
S-腺苷甲硫氨酸（SAM）是主要的甲基供体，具有广谱的靶底物。因此，它是几乎所有生物甲基化反应所必需的。SAM由甲硫氨酸腺苷转移酶从细胞质中的甲硫氨酸和ATP合成，随后分布在不同的细胞区室中，包括线粒体，其中甲基化主要是核酸修饰和代谢链功能所需的。我们报告了一个综合征在三个家庭的影响减少线粒体内甲基化引起的隐性突变的基因编码的唯一已知的线粒体SAM转运蛋白，SLC 25 A26。临床结果从呼吸功能不全和水肿导致的新生儿死亡到儿童期心肺衰竭和缓慢进行性肌无力的急性发作不等。我们发现，SLC 25 A26突变导致各种线粒体缺陷，包括影响RNA稳定性，蛋白质修饰，线粒体翻译，辅酶Q10和硫辛酸的生物合成。
S-adenosylmethionine (SAM) is the predominant methyl group donor and has a large spectrum of target substrates. As such, it is essential for nearly all biological methylation reactions. SAM is synthesized by methionine adenosyltransferase from methionine and ATP in the cytoplasm and subsequently distributed throughout the different cellular compartments, including mitochondria, where methylation is mostly required for nucleic-acid modifications and respiratory-chain function. We report a syndrome in three families affected by reduced intra-mitochondrial methylation caused by recessive mutations in the gene encoding the only known mitochondrial SAM transporter, SLC25A26. Clinical findings ranged from neonatal mortality resulting from respiratory insufficiency and hydrops to childhood acute episodes of cardiopulmonary failure and slowly progressive muscle weakness. We show that SLC25A26 mutations cause various mitochondrial defects, including those affecting RNA stability, protein modification, mitochondrial translation, and the biosynthesis of CoQ10 and lipoic acid.