ArticleCell reports2013
Inhibition of mitochondrial aconitase by succination in fumarate hydratase deficiency.
Article in Cell reports, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 101 papers.
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Who cites it
101 citing papers in PubMed, 156 citations in OpenAlex.
- Itaconation and Succination as Metabolite-Derived Cysteine Modifications in Inflammatory Signalling: Biochemical Mechanisms, Chemoproteomic Mapping, and Therapeutic Opportunities.Cell biochemistry and biophysics · 2026Review
- Metabolic regulation of calcium homeostasis via SERCA succination.Science advances · 2026Article
- Article
- Regulatory networks of iron sulfur cluster biology in cancer mechanisms and therapeutic perspectives.iScience · 2026Review
- Cysteine-S-nitrosylation inhibits Rop5-mediated immune evasion inbioRxiv : the preprint server for biology · 2025Article
- Aberrant S-nitrosylation in the TCA cycle contributes to mitochondrial dysfunction, energy compromise, and synapse loss in neurodegenerative diseases.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2025Review
- Metabolic Effects of the Cancer Metastasis Modulator MEMO1.Metabolites · 2025Article
- ADSL-generated fumarate binds and inhibits STING to promote tumour immune evasion.Nature cell biology · 2025Article
- Multiplexed longitudinal analysis of the cellular and microbial dynamics of acute polymicrobial sepsis in mice.Frontiers in immunology · 2025Article
- Reasons why life on Earth rarely makes fluorine-containing compounds and their implications for the search for life beyond Earth.Scientific reports · 2024Article
- Metabolic alterations in hereditary and sporadic renal cell carcinoma.Nature reviews. Nephrology · 2024Review
- Cardiometabolic Modulation by Semaglutide Contributes to Cardioprotection in Rats with Myocardial Infarction.Drug design, development and therapy · 2024Article
- The Tricarboxylic Acid Cycle Metabolites for Cancer: Friend or Enemy.Research (Washington, D.C.) · 2024Review
- Defective function of α-ketoglutarate dehydrogenase exacerbates mitochondrial ATP deficits during complex I deficiency.Redox biology · 2023Article
- Fumarate hydratase (FH) and cancer: a paradigm of oncometabolism.British journal of cancer · 2023Review
- FH Variant Pathogenicity Promotes Purine Salvage Pathway Dependence in Kidney Cancer.Cancer discovery · 2023Article
- The Pleiotropic Effects of Fumarate: From Mitochondrial Respiration to Epigenetic Rewiring and DNA Repair Mechanisms.Metabolites · 2023Review
- The Interplay between Dysregulated Metabolism and Epigenetics in Cancer.Biomolecules · 2023Review
- Adenylosuccinic Acid: An Orphan Drug with Untapped Potential.Pharmaceuticals (Basel, Switzerland) · 2023Article
- Singlet oxygen-induced signalling depends on the metabolic status of the Chlamydomonas reinhardtii cell.Communications biology · 2023Article
41 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
17 authors at 5 institutions in 4 countries.
Funding
Abstract
The gene encoding the Krebs cycle enzyme fumarate hydratase (FH) is mutated in hereditary leiomyomatosis and renal cell cancer (HLRCC). Loss of FH activity causes accumulation of intracellular fumarate, which can directly modify cysteine residues to form 2-succinocysteine through succination. We undertook a proteomic-based screen in cells and renal cysts from Fh1 (murine FH)-deficient mice and identified 94 protein succination targets. Notably, we identified the succination of three cysteine residues in mitochondrial Aconitase2 (ACO2) crucial for iron-sulfur cluster binding. We show that fumarate exerts a dose-dependent inhibition of ACO2 activity, which correlates with increased succination as determined by mass spectrometry, possibly by interfering with iron chelation. Importantly, we show that aconitase activity is impaired in FH-deficient cells. Our data provide evidence that succination, resulting from FH deficiency, targets and potentially alters the function of multiple proteins and may contribute to the dysregulated metabolism observed in HLRCC.
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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.