ArticleeLife2021
Disruption of the TCA cycle reveals an ATF4-dependent integration of redox and amino acid metabolism.
Article in eLife, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 87 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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
87 citing papers in PubMed, 119 citations in OpenAlex.
- Fumarate and Its Esters: Physiology, Pathology, Molecular Mechanisms, Diseases, and Therapy.MedComm · 2026Review
- A multilayered stress-response circuit: The mammalian mitochondrial UPR.The FEBS journal · 2026Review
- ATF4 orchestrates cancer hallmarks: Stress adaptation, metabolic reprogramming and immune suppression.iScience · 2026Review
- Elucidating the mechanism underlying incomplete immune recovery in people living with HIV through CD4⁺ and CD8⁺ T cell multi-omics.Molecular medicine (Cambridge, Mass.) · 2026Article
- PCBP1 orchestrates amino acid metabolism burst during the naïve-to-primed pluripotency transition.Stem cell reports · 2026Article
- Combined inhibition of de novo pyrimidine synthesis and ATR promotes ATF4-mediated cell death inHemaSphere · 2026Article
- Copper oxide nanoparticles: from EU-regulatory landscape and mechanistic toxicity towards a cuproptosis-linked adverse outcome pathway.Archives of toxicology · 2026Review
- Mitochondrial integrated stress response activation creates a therapeutic vulnerability to MCL-1 inhibition in acute myeloid leukemia.Cell death & disease · 2026Article
- ATF4 coordinates amino acid and nucleotide synthesis with selective protein translation to ensure proper DNA replication timing in leukemia cells.Nature communications · 2026Article
- Reverse engineering of BNIP3 identifies a mitochondrial protective peptide.Nature communications · 2026Article
- Transcription Factor ATF4 Deletion Reprograms Glucose Metabolism in Clear Cell Renal Cell Carcinoma.Cancers · 2026Article
- AMC-F1 regulates mitochondria-autophagy crosstalk independent of nutrient stress.Nature communications · 2026Article
- Leucyl tRNA synthetase ameliorates cholestatic liver injury by inhibiting integrated stress response in mice.Scientific reports · 2026Article
- Sex and social group altered the gut microbiome and fecal metabolome in the critically endangered Yangtze finless porpoise (Current zoology · 2026Article
- Heavy water labeling reveals metabolic flexibility of amino acid and polyamine pathways in mammalian cells.Communications chemistry · 2026Article
- The Effect of Angiotensin (1-7) on Serum Metabolomics in Obese Type 2 Diabetic Mice.Metabolites · 2026Article
- Para-dichlorobenzene inhibits Fusarium oxysporum f. sp. cubense tropical race 4 by inducing membrane damage, mitochondrial dysfunction, and transcriptional reprogramming.BMC microbiology · 2026Article
- Control of retrotransposon-driven activation of the interferon response by the double-stranded RNA binding protein DGCR8.Nucleic acids research · 2026Article
- Advancements in somatic mutation detection through loop-mediated isothermal amplification (LAMP) in human tumors.Journal of applied genetics · 2026Review
- Review
27 more citing papers are in PubMed but not listed here.
Corrections and comments
- Commented on by
Authors and funding
14 authors at 2 institutions in 1 country.
Funding
Abstract
The Tricarboxylic Acid (TCA) Cycle is arguably the most critical metabolic cycle in physiology and exists as an essential interface coordinating cellular metabolism, bioenergetics, and redox homeostasis. Despite decades of research, a comprehensive investigation into the consequences of TCA cycle dysfunction remains elusive. Here, we targeted two TCA cycle enzymes, fumarate hydratase (FH) and succinate dehydrogenase (SDH), and combined metabolomics, transcriptomics, and proteomics analyses to fully appraise the consequences of TCA cycle inhibition (TCAi) in murine kidney epithelial cells. Our comparative approach shows that TCAi elicits a convergent rewiring of redox and amino acid metabolism dependent on the activation of ATF4 and the integrated stress response (ISR). Furthermore, we also uncover a divergent metabolic response, whereby acute FHi, but not SDHi, can maintain asparagine levels via reductive carboxylation and maintenance of cytosolic aspartate synthesis. Our work highlights an important interplay between the TCA cycle, redox biology, and amino acid homeostasis.
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.