Mitochondrial tRNA modifications: functions, diseases caused by their loss, and treatment strategies

被引：0
作者：
Chujo, Takeshi [1 ]
Tomizawa, Kazuhito [1 ]
机构：
[1] Kumamoto Univ, Fac Life Sci, Dept Mol Physiol, Kumamoto 8608556, Japan
来源：
RNA | 2025年 / 31卷 / 03期
基金：
日本科学技术振兴机构; 日本学术振兴会;
关键词：
tRNA modification; mitochondrial disease; tRNA modopathy; MELAS; mitoTALEN; WOBBLE MODIFICATION DEFICIENCY; STROKE-LIKE EPISODES; MUTANT TRANSFER-RNAS; LACTIC-ACIDOSIS; 1ST POSITION; HYPERTROPHIC CARDIOMYOPATHY; MODIFICATION DEFECT; MYOCLONIC EPILEPSY; BASE MODIFICATIONS; CLINICAL-FEATURES;
D O I：
10.1261/rna.080257.124
中图分类号：
Q5 [生物化学]; Q7 [分子生物学];
学科分类号：
071010 ; 081704 ;
摘要：
Mitochondrial tRNA (mt-tRNA) modifications play pivotal roles in decoding and sustaining tRNA stability, thereby enabling the synthesis of essential respiratory complex proteins in mitochondria. Consequently, loss of human mt-tRNA modifications caused by mutations in the mitochondrial or nuclear genome can cause life-threatening mitochondrial diseases such as encephalopathy and cardiomyopathy. In this article, we first provide a comprehensive overview of the functions of mt-tRNA modifications, the responsible modification enzymes, and the diseases caused by the loss of mt-tRNA modifications. We then discuss progress and potential strategies to treat these diseases, including taurine supplementation for MELAS patients, targeted deletion of mtDNA variants, and overexpression of modification-related proteins. Finally, we discuss factors that need to be overcome to cure "mitochondrial tRNA modopathies."
引用
收藏
页码：382 / 394
页数：13
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