Physiological role of mitochondrial tRNA modification

2017 Fiscal Year Final Research Report

• Project/Area Number: 15K08178
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: General physiology
• Research Institution: Kumamoto University
• Principal Investigator: Wei Fan-Yan 熊本大学, 大学院生命科学研究部(医), 准教授 (90555773)
• Research Collaborator: Mohri Satoshi
• Project Period (FY): 2015-04-01 – 2018-03-31
• Keywords: 代謝 / ミトコンドリア / RNA / 修飾

Outline of Final Research Achievements

In this study, we report that Cdk5 regulatory subunit-associated protein 1 (Cdk5rap1) is responsible for 2-methylthio (ms2) modifications of mammalian mt-tRNAs for Ser(UCN), Phe, Tyr and Trp codons. Deficiency in ms2 modification markedly impaired mitochondrial protein synthesis, which resulted in respiratory defects in Cdk5rap1 knockout (KO) mice. The KO mice were highly susceptive to stress-induced mitochondrial remodelling and exhibited accelerated myopathy and cardiac dysfunction under stressed conditions. Furthermore, we demonstrate that the ms2 modifications of mt-tRNAs were sensitive to oxidative stress and were reduced in patients with mitochondrial disease. These findings highlight the fundamental role of ms2 modifications of mt-tRNAs in mitochondrial protein synthesis and their pathological consequences in mitochondrial disease.

Free Research Field

生理学