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Updated: Jun 4, 2025

Author Spotlight: Decoding Mitochondrial Aging
Published on: June 30, 2023
Mitochondrial tRNA modifications: functions, diseases caused by their loss, and treatment strategies
Takeshi Chujo1, Kazuhito Tomizawa2
1Department of Molecular Physiology, Faculty of Life Sciences, Kumamoto University, Kumamoto 860-8556, Japan tchujo@kumamoto-u.ac.jp.
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."
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