LAUSR

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.”