A mitochondrial myopathy-associated tRNASer(UCN) 7453G>A mutation alters tRNA metabolism and mitochondrial function.

Abstract

BACKGROUND:

Mitochondrial disorders are a group of heterogeneous diseases characterized by biochemical disturbances in oxidative phosphorylation (OXPHOS). Mutations in mitochondrial transfer RNA (mt-tRNA) genes are the most frequently in mitochondrial disease. However, few studies have detailed the molecular mechanisms behind these mutations.

METHODS:

We performed clinical evaluation, genetic analysis, muscle histochemistry, and molecular and biochemical investigations in muscle tissue and proband-derived cybrid cell lines.

RESULTS:

We found a mitochondrial tRNASer(UCN) mutation (m.7453G>A) in a 15-year-old patient with severe mitochondrial myopathy. We demonstrated that this mutation caused impairment of mitochondrial translation, respiratory deficiency, overproduction of reactive oxygen species (ROS), and decreased mitochondrial membrane potential (MMP), which ultimately led to severe mitochondrial myopathy.

CONCLUSION:

Our findings offer valuable new insights into the tRNASer(UCN) m.7453G>A mutation for both the pathogenic mechanism and functional consequences.

• Authors: Yan Lin, Xuebi Xu, Wei Wang, Fuchen Liu, Dandan Zhao, Duoling Li, Kunqian Ji, Wei Li, Yuying Zhao, Chuanzhu Yan
• Journal: Mitochondrion (Mitochondrion) Vol. 57 Pg. 1-8 (03 2021) ISSN: 1872-8278 [Electronic] Netherlands
• PMID: 33279600 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2020 Elsevier B.V. and Mitochondria Research Society. All rights reserved.

Chemical References

• RNA, Transfer, Ser
• Reactive Oxygen Species

Topics

• Adolescent
• Cell Line
• Female
• Genome, Mitochondrial
• High-Throughput Nucleotide Sequencing
• Humans
• Membrane Potential, Mitochondrial
• Mitochondrial Myopathies (genetics, metabolism)
• Models, Molecular
• Nucleic Acid Conformation
• Polymorphism, Single Nucleotide
• Protein Biosynthesis
• RNA, Transfer, Ser (chemistry, genetics)
• Reactive Oxygen Species (metabolism)
• Sequence Analysis, DNA (methods)