ArticleScientific reports2018
Defects in the mitochondrial-tRNA modification enzymes MTO1 and GTPBP3 promote different metabolic reprogramming through a HIF-PPARγ-UCP2-AMPK axis.
Article in Scientific reports, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers, 1 of them a synthesis that pooled it.
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Who cites it
19 citing papers in PubMed, 1 synthesis or guideline pooled it, 28 citations in OpenAlex.
- Pathogenicity Analysis of a Novel Variant inGenes · 2023Pooled it
- Review
- Mitochondrial translational control in cardiovascular diseases: from mechanisms to therapies.Redox biology · 2026Review
- tRNA modifications in cancer: from molecular mechanisms to clinical translation.Biomarker research · 2026Review
- Building a credibility-based framework for target discovery: Perspectives from tRNA synthetase-linked metabolic diseases.Briefings in bioinformatics · 2026Article
- Endothelial GTPBP3 directs developmental angiogenesis and neovascularization after limb ischemia via the mtROS/HRl/ATF4/mTORC1 axis.Angiogenesis · 2025Article
- [Abnormal transfer RNA epigenetic modifications and related impact on neurodegenerative diseases].Zhejiang da xue xue bao. Yi xue ban = Journal of Zhejiang University. Medical sciences · 2024Review
- The role of peroxisome proliferator-activated receptors in the tumor microenvironment, tumor cell metabolism, and anticancer therapy.Frontiers in pharmacology · 2023Review
- Hypoxia-Inducible Factor 1 and Mitochondria: An Intimate Connection.Biomolecules · 2022Review
- A novel splice variant of Elp3/Kat9 regulates mitochondrial tRNA modification and function.Scientific reports · 2022Article
- Metformin Attenuates Cardiac HypertrophyFrontiers in pharmacology · 2022Article
- Human Mitochondrial RNA Processing and Modifications: Overview.International journal of molecular sciences · 2021Review
- Review
- The effects of UCP2 on autophagy through the AMPK signaling pathway in septic cardiomyopathy and the underlying mechanism.Annals of translational medicine · 2021Article
- Novel Mutations in theFrontiers in genetics · 2021Article
- tRNA cleavage: a new insight.Neural regeneration research · 2020Review
- Proteomic and Metabolomic Analyses Provide Insights into the Mechanism on Arginine Metabolism Regulated by tRNA Modification Enzymes GidA and MnmE ofFrontiers in cellular and infection microbiology · 2020Article
- Role of purines in regulation of metabolic reprogramming.Purinergic signalling · 2019Review
- Impact of tRNA Modifications and tRNA-Modifying Enzymes on Proteostasis and Human Disease.International journal of molecular sciences · 2018Review
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Authors and funding
8 authors at 5 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Human proteins MTO1 and GTPBP3 are thought to jointly catalyze the modification of the wobble uridine in mitochondrial tRNAs. Defects in each protein cause infantile hypertrophic cardiomyopathy with lactic acidosis. However, the underlying mechanisms are mostly unknown. Using fibroblasts from an MTO1 patient and MTO1 silenced cells, we found that the MTO1 deficiency is associated with a metabolic reprogramming mediated by inactivation of AMPK, down regulation of the uncoupling protein 2 (UCP2) and transcription factor PPARγ, and activation of the hypoxia inducible factor 1 (HIF-1). As a result, glycolysis and oxidative phosphorylation are uncoupled, while fatty acid metabolism is altered, leading to accumulation of lipid droplets in MTO1 fibroblasts. Unexpectedly, this response is different from that triggered by the GTPBP3 defect, as GTPBP3-depleted cells exhibit AMPK activation, increased levels of UCP2 and PPARγ, and inactivation of HIF-1. In addition, fatty acid oxidation and respiration are stimulated in these cells. Therefore, the HIF-PPARγ-UCP2-AMPK axis is operating differently in MTO1- and GTPBP3-defective cells, which strongly suggests that one of these proteins has an additional role, besides mitochondrial-tRNA modification. This work provides new and useful information on the molecular basis of the MTO1 and GTPBP3 defects and on putative targets for therapeutic intervention.
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