ArticleNature2018
Mitochondrial translation requires folate-dependent tRNA methylation.
Article in Nature, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT03850314 (The Effects of Glycine on Atherosclerosis and Metabolic Syndrome-related Parameters), which is not on this map. Cited by 176 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
The Effects of Glycine on Atherosclerosis and Metabolic Syndrome-related Parameters: A Clinical and Ex-vivo Study.
Who cites it
176 citing papers in PubMed, 265 citations in OpenAlex.
- Folate metabolism in tumor-associated macrophages drives immunosuppressive function to promote tumor growth.bioRxiv : the preprint server for biology · 2026Article
- Review
- Covalent Inhibition of SHMT2 by Gambogic Acid Induces Ferroptosis Through Mitochondrial Collapse in Triple-Negative Breast Cancer.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Programmable aging function-related mitochondrial DNA 5-methylcytosine (m5C) modification with a TALE-directed methyltransferase.Cell communication and signaling : CCS · 2026Article
- Mechanisms and disease relevance of mitochondrial translation in humans.Nature reviews. Molecular cell biology · 2026Review
- MTHFD2: a promising metabolic checkpoint for diseases.Journal of translational medicine · 2026Review
- Serine Hydroxymethyltransferase (SHMT) in biology and disease: molecular mechanisms and therapeutic targeting.Journal of translational medicine · 2026Review
- Article
- SHMT2 inhibition triggers mitochondrial apoptosis to suppress lung adenocarcinoma progression.Journal of translational medicine · 2026Article
- Mitochondrial metabolism restoration via Tramiprosate suppresses mitochondrial ROS-driven foamy macrophage senescence post spinal cord injury.Journal of orthopaedic translation · 2026Article
- SLC6A6 imports taurine into mitochondria to sustain mitochondrial translation and tumour growth.Nature metabolism · 2026Article
- mAdvanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- How tailored Ribo-seq methods probe unique translation events.RNA (New York, N.Y.) · 2026Review
- Mitochondria: from powerhouses of cells to hubs in antitumor immunity.Frontiers in immunology · 2026Review
- A Nonketotic Hyperglycinemia Mouse Shows Wide-Ranging Biochemical Consequences of Elevated Glycine, Reduced Folate One-Carbon Charging, and Serine Deficiency.Journal of inherited metabolic disease · 2026Article
- Spatiotemporal control of mitoribosome-mediated metabolic reprogramming in cancer: implications for heterogeneity and therapeutic targeting.Frontiers in cell and developmental biology · 2026Review
- Research on serine hydroxymethyltransferase 2 mechanisms in malignant tumor development and progression.PeerJ · 2026Review
- Complexes Formed by the K63-Specific Deubiquitinating Enzyme BRCC36: New Promising Therapeutic Targets in Human Disease.Biomolecules · 2025Review
- Photocatalytic labelling-enabled subcellular-resolved RNA profiling and synchronous multi-omics investigation.Nature chemistry · 2025Article
- Effects of aging and anti-aging dietary restriction on regulators of the [NADPH]/[NADPFree radical biology & medicine · 2025Review
116 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 3 institutions in 2 countries.
Funding
Abstract
Folates enable the activation and transfer of one-carbon units for the biosynthesis of purines, thymidine and methionine. Antifolates are important immunosuppressive and anticancer agents. In proliferating lymphocytes and human cancers, mitochondrial folate enzymes are particularly strongly upregulated. This in part reflects the need for mitochondria to generate one-carbon units and export them to the cytosol for anabolic metabolism. The full range of uses of folate-bound one-carbon units in the mitochondrial compartment itself, however, has not been thoroughly explored. Here we show that loss of the catalytic activity of the mitochondrial folate enzyme serine hydroxymethyltransferase 2 (SHMT2), but not of other folate enzymes, leads to defective oxidative phosphorylation in human cells due to impaired mitochondrial translation. We find that SHMT2, presumably by generating mitochondrial 5,10-methylenetetrahydrofolate, provides methyl donors to produce the taurinomethyluridine base at the wobble position of select mitochondrial tRNAs. Mitochondrial ribosome profiling in SHMT2-knockout human cells reveals that the lack of this modified base causes defective translation, with preferential mitochondrial ribosome stalling at certain lysine (AAG) and leucine (UUG) codons. This results in the impaired expression of respiratory chain enzymes. Stalling at these specific codons also occurs in certain inborn errors of mitochondrial metabolism. Disruption of whole-cell folate metabolism, by either folate deficiency or antifolate treatment, also impairs the respiratory chain. In summary, mammalian mitochondria use folate-bound one-carbon units to methylate tRNA, and this modification is required for mitochondrial translation and thus oxidative phosphorylation.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.