Molecular pathogenesis and gene therapy-based intervention of GTPBP3-related mitochondrial disease - PubMed
6 hours ago
- #Gene therapy
- #GTPBP3 mutations
- #Mitochondrial disease
- The study identifies two genetic variants (c.689 A > C (p.Q230P) and c.1120 A > G (p.N374D)) of GTPBP3 in a Chinese proband with metabolic disorders and multisystem dysfunction.
- These mutations cause protein multimerization/aggregation, protease degradation, decreased GTPase activity, and reduced tRNA modification, leading to mitochondrial translation and functional issues.
- In mice, homozygous N374D mutations result in embryonic lethality, while homozygous E230P or compound heterozygous E230P/N374D knock-in mice develop cardiac and muscular dysfunction.
- Mitochondrial dysfunction and pathology can be reversed by virus-mediated GTPBP3 expression in both cells and animals.
- This research offers insights into the etiology and potential intervention strategies for GTPBP3-related mitochondrial diseases.