ArticleCell reports2019
Disrupting Mitochondrial Pyruvate Uptake Directs Glutamine into the TCA Cycle away from Glutathione Synthesis and Impairs Hepatocellular Tumorigenesis.
Article in Cell reports, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 53 papers.
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The trial behind it
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Who cites it
53 citing papers in PubMed, 81 citations in OpenAlex.
- Glutamine metabolism in health and disease.Signal transduction and targeted therapy · 2026Review
- Regulation of Autophagy and Metabolism in Hepatocellular Carcinoma: Involvement of Wnt-β-Catenin Pathway.Journal of cellular and molecular medicine · 2026Article
- Dysbiotic Microbiome-Metabolome Axis in Childhood Obesity and Metabolic Syndrome.Journal of dental research · 2025Article
- Hesperetin Protects from Palmitic-Acid-Induced Lipotoxicity through the Inhibition of Glutaminolysis, mTORC1 Signaling, and Limited Apoptosis.Journal of agricultural and food chemistry · 2025Article
- Targeting pyruvate metabolism generates distinct CD8+ T cell responses to gammaherpesvirus and B lymphoma.JCI insight · 2025Article
- Immunometabolism and oxidative stress: roles and therapeutic strategies in cancer and aging.npj aging · 2025Review
- Molecular basis of pyruvate transport and inhibition of the human mitochondrial pyruvate carrier.Science advances · 2025Article
- Glutathione determines chronic myeloid leukemia vulnerability to an inhibitor of CMPK and TMPK.Communications biology · 2024Article
- Fluoride impairs vascular smooth muscle A7R5 cell lines via disrupting amino acids metabolism.Journal of translational medicine · 2024Article
- Glutamine metabolism, a double agent combating or fuelling hepatocellular carcinoma.JHEP reports : innovation in hepatology · 2024Review
- Article
- Prostate lineage-specific metabolism governs luminal differentiation and response to antiandrogen treatment.Nature cell biology · 2023Article
- Hepatic pyruvate and alanine metabolism are critical and complementary for maintenance of antioxidant capacity and resistance to oxidative insult.Molecular metabolism · 2023Article
- Monocarboxylate Transporter-1 (MCT1)-Mediated Lactate Uptake Protects Pancreatic Adenocarcinoma Cells from Oxidative Stress during Glutamine Scarcity Thereby Promoting Resistance against Inhibitors of Glutamine Metabolism.Antioxidants (Basel, Switzerland) · 2023Article
- [Comparative analysis of intestinal microbiota distribution characteristics based on metagenomics in patients with hepatitis B cirrhosis with or without ascites].Zhonghua gan zang bing za zhi = Zhonghua ganzangbing zazhi = Chinese journal of hepatology · 2023Article
- Disposition and metabolomic effects of 2,2',5,5'-tetrachlorobiphenyl in female rats following intraperitoneal exposure.Environmental toxicology and pharmacology · 2023Article
- Disposition and Metabolomic Effects of 2,2',5,5'-Tetrachlorobiphenyl in Female Rats Following Intraperitoneal Exposure.bioRxiv : the preprint server for biology · 2023Article
- Fifty years of the mitochondrial pyruvate carrier: New insights into its structure, function, and inhibition.Acta physiologica (Oxford, England) · 2023Review
- The mitochondrial pyruvate carrier complex potentiates the efficacy of proteasome inhibitors in multiple myeloma.Blood advances · 2023Article
- The Hepatic Mitochondrial Pyruvate Carrier as a Regulator of Systemic Metabolism and a Therapeutic Target for Treating Metabolic Disease.Biomolecules · 2023Review
Corrections and comments
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Authors and funding
15 authors at 1 institution in 1 country.
Funding
Abstract
Hepatocellular carcinoma (HCC) is a devastating cancer increasingly caused by non-alcoholic fatty liver disease (NAFLD). Disrupting the liver Mitochondrial Pyruvate Carrier (MPC) in mice attenuates NAFLD. Thus, we considered whether liver MPC disruption also prevents HCC. Here, we use the N-nitrosodiethylamine plus carbon tetrachloride model of HCC development to test how liver-specific MPC knock out affects hepatocellular tumorigenesis. Our data show that liver MPC ablation markedly decreases tumorigenesis and that MPC-deficient tumors transcriptomically downregulate glutathione metabolism. We observe that MPC disruption and glutathione depletion in cultured hepatomas are synthetically lethal. Stable isotope tracing shows that hepatocyte MPC disruption reroutes glutamine from glutathione synthesis into the tricarboxylic acid (TCA) cycle. These results support a model where inducing metabolic competition for glutamine by MPC disruption impairs hepatocellular tumorigenesis by limiting glutathione synthesis. These findings raise the possibility that combining MPC disruption and glutathione stress may be therapeutically useful in HCC and additional cancers.
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Registered trials
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