ArticleCell death & disease2023
Pyruvate transamination and NAD biosynthesis enable proliferation of succinate dehydrogenase-deficient cells by supporting aerobic glycolysis.
Article in Cell death & disease, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 26 citations in OpenAlex.
- Shotgun proteomic analysis of quail liver under feed deprivation and low-energy diet conditions.Veterinary and animal science · 2026Article
- Expansion of Germline Variants in Primary Hyperparathyroidism: Fumarate Hydratase Deficiency as a Cause of Parathyroid Adenomas.Endocrine pathology · 2026Observational
- Regulation of mitochondrial iron homeostasis in tumor cells.Molecular medicine (Cambridge, Mass.) · 2026Review
- Hepatic mitochondrial signaling as a systemic hub: inter-organ communication networks in aging and aging-related diseases.Frontiers in cell and developmental biology · 2026Review
- Metabolic Effects of Succinate Dehydrogenase Loss in Cancer.Journal of cellular physiology · 2025Review
- ANXA2 in cancer: aberrant regulation of tumour cell apoptosis and its immune interactions.Cell death discovery · 2025Review
- Targeting HVEM-GPT2 axis: a novel approach to T cell activation and metabolic reprogramming in non-small cell lung cancer therapy.Cancer immunology, immunotherapy : CII · 2025Article
- Advances in the Development of Mitochondrial Pyruvate Carrier Inhibitors for Therapeutic Applications.Biomolecules · 2025Review
- NAMPT Impairs Vascular Permeability in Periodontitis by Influencing FASN-mediated Lipogenesis.International journal of biological sciences · 2025Article
- The Ku70-SIX1-GPT2 axis regulates alpha-ketoglutarate metabolism to drive progression of prostate cancer.Oncogene · 2025Article
- Dual activation of GCGR/GLP1R signaling ameliorates intestinal fibrosisActa pharmaceutica Sinica. B · 2025Article
- Experimental study on the treatment of norepinephrine transporter-overexpressing pheochromocytomas and paragangliomas: a synthetic lethality strategy combiningFrontiers in oncology · 2025Article
- Similar deficiencies, different outcomes: succinate dehydrogenase loss in adrenal medulla vs. fibroblast cell culture models of paraganglioma.Cancer & metabolism · 2024Article
- Succinate Dehydrogenase and Human Disease: Novel Insights into a Well-Known Enzyme.Biomedicines · 2024Review
- Stable Isotope Tracing Analysis in Cancer Research: Advancements and Challenges in Identifying Dysregulated Cancer Metabolism and Treatment Strategies.Metabolites · 2024Review
- Focus on Mitochondrial Respiratory Chain: Potential Therapeutic Target for Chronic Renal Failure.International journal of molecular sciences · 2024Review
- Novel Approaches to the Establishment of Local Microenvironment from Resorbable Biomaterials in the Brain In Vitro Models.International journal of molecular sciences · 2023Review
- Neuroprotective Effects and Therapeutic Potential of Dichloroacetate: Targeting Metabolic Disorders in Nervous System Diseases.International journal of nanomedicine · 2023Review
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 2 countries.
Funding
Abstract
Succinate dehydrogenase (SDH) is the mitochondrial enzyme converting succinate to fumarate in the tricarboxylic acid (TCA) cycle. SDH acts as a tumor suppressor with germline loss-of-function mutations in its encoding genes predisposing to aggressive familial neuroendocrine and renal cancer syndromes. Lack of SDH activity disrupts the TCA cycle, imposes Warburg-like bioenergetic features, and commits cells to rely on pyruvate carboxylation for anabolic needs. However, the spectrum of metabolic adaptations enabling SDH-deficient tumors to cope with a dysfunctional TCA cycle remains largely unresolved. By using previously characterized Sdhb-deleted kidney mouse cells, here we found that SDH deficiency commits cells to rely on mitochondrial glutamate-pyruvate transaminase (GPT2) activity for proliferation. We showed that GPT2-dependent alanine biosynthesis is crucial to sustain reductive carboxylation of glutamine, thereby circumventing the TCA cycle truncation determined by SDH loss. By driving the reductive TCA cycle anaplerosis, GPT2 activity fuels a metabolic circuit maintaining a favorable intracellular NAD
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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.