线粒体tRNA修饰：功能、因修饰缺失导致的疾病及治疗策略。

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

作者信息

Chujo Takeshi, Tomizawa Kazuhito

机构信息

Department of Molecular Physiology, Faculty of Life Sciences, Kumamoto University, Kumamoto 860-8556, Japan

Department of Molecular Physiology, Faculty of Life Sciences, Kumamoto University, Kumamoto 860-8556, Japan.

出版信息

RNA. 2025 Feb 19;31(3):382-394. doi: 10.1261/rna.080257.124.

DOI:10.1261/rna.080257.124

PMID:39719325

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11874988/

Abstract

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."

摘要

线粒体转运RNA（mt-tRNA）修饰在解码和维持tRNA稳定性方面发挥着关键作用，从而使得线粒体中必需的呼吸复合物蛋白得以合成。因此，线粒体或核基因组中的突变导致的人类mt-tRNA修饰缺失可引发危及生命的线粒体疾病，如脑病和心肌病。在本文中，我们首先全面概述了mt-tRNA修饰的功能、负责修饰的酶以及由mt-tRNA修饰缺失引起的疾病。然后，我们讨论了治疗这些疾病的进展和潜在策略，包括对线粒体脑肌病伴乳酸血症和卒中样发作（MELAS）患者补充牛磺酸、靶向删除线粒体DNA（mtDNA）变体以及过表达与修饰相关的蛋白质。最后，我们讨论了治愈“线粒体tRNA修饰病”需要克服的因素。