ArticleThe Journal of experimental medicine2020
Nicotinamide nucleotide transhydrogenase regulates mitochondrial metabolism in NSCLC through maintenance of Fe-S protein function.
Article in The Journal of experimental medicine, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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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.
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Who cites it
27 citing papers in PubMed, 51 citations in OpenAlex.
- Article
- Nicotinamide nucleotide transhydrogenase directly couples redox homeostasis to proline biosynthesis in human glioma.Molecular cell · 2026Article
- Multi-modal molecular and spatial profiling reveals NNT as a prognostic biomarker in obesity-associated colorectal cancer.Journal of gastroenterology · 2026Article
- NFS1 Regulates IDH2 to Attenuate Abdominal Aortic Aneurysms via Interacting With SP2.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Cancer progression through the lens of age-induced metabolic reprogramming.Nature reviews. Cancer · 2025Review
- Recommendations for robust and reproducible research on ferroptosis.Nature reviews. Molecular cell biology · 2025Review
- Glucosamine-Mediated Hexosamine Biosynthesis Pathway Activation Uses ATF4 to Promote "Exercise-Like" Angiogenesis and Perfusion Recovery in PAD.Circulation · 2024Article
- Homeostatic regulation of NAD(H) and NADP(H) in cells.Genes & diseases · 2024Review
- The Cancer Antioxidant Regulation System in Therapeutic Resistance.Antioxidants (Basel, Switzerland) · 2024Review
- Mitochondrial respiratory function is preserved under cysteine starvation via glutathione catabolism in NSCLC.Nature communications · 2024Article
- NFS1 as a Candidate Prognostic Biomarker for Gastric Cancer Correlated with Immune Infiltrates.International journal of general medicine · 2024Article
- NADPH Dynamics: Linking Insulin Resistance and β-Cells Ferroptosis in Diabetes Mellitus.International journal of molecular sciences · 2023Review
- Molecular Mechanisms of IL18 in Disease.International journal of molecular sciences · 2023Review
- Toward a Unifying Hypothesis for Redesigned Lipid Catabolism as a Clinical Target in Advanced, Treatment-Resistant Carcinomas.International journal of molecular sciences · 2023Review
- Uncovering the IL-1β-PCAF-NNT axis: A new player in ferroptosis and tumor immune evasion.Cancer communications (London, England) · 2023Article
- UDP-glucose pyrophosphorylase as a target for regulating carbon flux distribution and antioxidant capacity in Phaeodactylum tricornutum.Communications biology · 2023Article
- Antisense lncRNA NNT-AS1 promoted esophageal squamous cell carcinoma progression by regulating its sense gene NNT expression.Cell death discovery · 2022Article
- Tff3 Deficiency Protects against Hepatic Fat Accumulation after Prolonged High-Fat Diet.Life (Basel, Switzerland) · 2022Article
- A CRISPR screen identifies redox vulnerabilities for KEAP1/NRF2 mutant non-small cell lung cancer.Redox biology · 2022Article
- Regulation of immune cell function by nicotinamide nucleotide transhydrogenase.American journal of physiology. Cell physiology · 2022Review
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
Human lung tumors exhibit robust and complex mitochondrial metabolism, likely precipitated by the highly oxygenated nature of pulmonary tissue. As ROS generation is a byproduct of this metabolism, reducing power in the form of nicotinamide adenine dinucleotide phosphate (NADPH) is required to mitigate oxidative stress in response to this heightened mitochondrial activity. Nicotinamide nucleotide transhydrogenase (NNT) is known to sustain mitochondrial antioxidant capacity through the generation of NADPH; however, its function in non-small cell lung cancer (NSCLC) has not been established. We found that NNT expression significantly enhances tumor formation and aggressiveness in mouse models of lung tumor initiation and progression. We further show that NNT loss elicits mitochondrial dysfunction independent of substantial increases in oxidative stress, but rather marked by the diminished activities of proteins dependent on resident iron-sulfur clusters. These defects were associated with both NADPH availability and ROS accumulation, suggesting that NNT serves a specific role in mitigating the oxidation of these critical protein cofactors.
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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.