Cited by 1,114Folate and B Vitamins ResearchCancer, Hypoxia, and MetabolismBiochemical and Molecular Research

The DOI matches its Crossref record; 41 of the 41 references it cites were found in a registry or an index.

Quantitative flux analysis reveals folate-dependent NADPH production

Open access

Fan, Jing, Ye, Jiangbin, Kamphorst, Jurre J., Shlomi, Tomer, Thompson, Craig B., Rabinowitz, Joshua D.·2014·Nature

Open this paper in CoChat — free account

Abstract

ATP is the dominant energy source in animals for mechanical and electrical work (for example, muscle contraction or neuronal firing). For chemical work, there is an equally important role for NADPH, which powers redox defence and reductive biosynthesis. The most direct route to produce NADPH from glucose is the oxidative pentose phosphate pathway, with malic enzyme sometimes also important. Although the relative contribution of glycolysis and oxidative phosphorylation to ATP production has been extensively analysed, similar analysis of NADPH metabolism has been lacking. Here we demonstrate the ability to directly track, by liquid chromatography-mass spectrometry, the passage of deuterium from labelled substrates into NADPH, and combine this approach with carbon labelling and mathematical modelling to measure NADPH fluxes. In proliferating cells, the largest contributor to cytosolic NADPH is the oxidative pentose phosphate pathway. Surprisingly, a nearly comparable contribution comes from serine-driven one-carbon metabolism, in which oxidation of methylene tetrahydrofolate to 10-formyl-tetrahydrofolate is coupled to reduction of NADP(+) to NADPH. Moreover, tracing of mitochondrial one-carbon metabolism revealed complete oxidation of 10-formyl-tetrahydrofolate to make NADPH. As folate metabolism has not previously been considered an NADPH producer, confirmation of its functional significance was undertaken through knockdown of methylenetetrahydrofolate dehydrogenase (MTHFD) genes. Depletion of either the cytosolic or mitochondrial MTHFD isozyme resulted in decreased cellular NADPH/NADP(+) and reduced/oxidized glutathione ratios (GSH/GSSG) and increased cell sensitivity to oxidative stress. Thus, although the importance of folate metabolism for proliferating cells has been long recognized and attributed to its function of producing one-carbon units for nucleic acid synthesis, another crucial function of this pathway is generating reducing power.

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

Integrity signals

Registry

Crossref · 10.1038/nature13236

Cites

41 of 41 references verified0 citation errors · 0 not checkable

Statistics

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Understanding the Warburg Effect: The Metabolic Requirements of Cell Proliferation
Vander Heiden, M. G., Cantley, L. C., & Thompson, C. B. (2009) · Science · doi:10.1126/science.1160809 · Cited by 16,197
Self-citation
On the origin of cancer cells
Warburg, O. (1956) · Science · doi:10.1126/science.123.3191.309 · Cited by 13,425
Glutamine supports pancreatic cancer growth through a KRAS-regulated metabolic pathway
Son, J., Lyssiotis, C. A., Ying, H., Wang, X., Hua, S., Ligorio, M., Perera, R. M., Ferrone, C. R., Mullarky, E., Shyh-Chang, N., et al. (2013) · Nature · doi:10.1038/nature12040 · Cited by 1,990
Functional genomics reveal that the serine synthesis pathway is essential in breast cancer
Possemato, R., Marks, K. M., Shaul, Y. D., Pacold, M. E., Kim, D., Birsoy, K., Sethumadhavan, S., Woo, H.-K., Jang, H. G., Jha, A. K., et al. (2011) · Nature · doi:10.1038/nature10350 · Cited by 1,683
Metabolite profiling identifies a key role for glycine in rapid cancer cell proliferation
Jain, M., Nilsson, R., Sharma, S., Madhusudhan, N., Kitami, T., Souza, A. L., Kafri, R., Kirschner, M. W., Clish, C. B., & Mootha, V. K. (2012) · Science · doi:10.1126/science.1218595 · Cited by 1,403
Identification of ROS Using Oxidized DCFDA and Flow-Cytometry
Eruslanov, E. B., & Kusmartsev, S. A. (2009) · Methods in molecular biology · doi:10.1007/978-1-60761-411-1_4 · Cited by 1,376
Global reconstruction of the human metabolic network based on genomic and bibliomic data
Duarte, N. C., Becker, S. A., Jamshidi, N., Thiele, I., Mo, M. L., Vo, T. D., Srivas, R., & Palsson, B. Ø. (2007) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0610772104 · Cited by 1,374
Inhibition of Pyruvate Kinase M2 by Reactive Oxygen Species Contributes to Cellular Antioxidant Responses
Anastasiou, D., Poulogiannis, G., Asara, J. M., Boxer, M. B., Jiang, J., Shen, M., Bellinger, G., Sasaki, A. T., Locasale, J. W., Auld, D. S., et al. (2011) · Science · doi:10.1126/science.1211485 · Cited by 1,218
Phosphoglycerate dehydrogenase diverts glycolytic flux and contributes to oncogenesis
Locasale, J. W., Grassian, A. R., Melman, T., Lyssiotis, C. A., Mattaini, K. R., Bass, A. J., Heffron, G., Metallo, C. M., Muranen, T., Sharfi, H., et al. (2011) · Nature Genetics · doi:10.1038/ng.890 · Cited by 1,120
Serine starvation induces stress and p53-dependent metabolic remodelling in cancer cells
Maddocks, O. D. K., Berkers, C. R., Mason, S. M., Zheng, L., Blyth, K., Gottlieb, E., & Vousden, K. H. (2013) · Nature · doi:10.1038/nature11743 · Cited by 1,007

Flagged first, then by citations

Show all 41 references

Sorted by citations

Items 401–500 of 1,000

Unraveling the role of the mitochondrial one-carbon pathway in undifferentiated thyroid cancer by multi-omics analyses
Lee, S. E., Park, S., Yi, S., Choi, N. R., Lim, M. A., Chang, J. W., Won, H.-R., Kim, J. R., Ko, H. M., Chung, E., et al. (2024) · Nature Communications · doi:10.1038/s41467-024-45366-0 · Cited by 46
Metabolomic profiling of hormone-dependent cancers: a bird's eye view
Lloyd, S. M., Arnold, J. M., & Sreekumar, A. (2015) · Trends in Endocrinology and Metabolism · doi:10.1016/j.tem.2015.07.001 · Cited by 48
Elucidation of the growth delimitation of Dunaliella tertiolecta under nitrogen stress by integrating transcriptome and peptidome analysis
Shin, H., Hong, S.-J., Kim, H., Yoo, C., Lee, H., Choi, H., Lee, C., & Cho, B. (2015) · Bioresource Technology · doi:10.1016/j.biortech.2015.07.002 · Cited by 45
PHGDH preserves one-carbon cycle to confer metabolic plasticity in chemoresistant gastric cancer during nutrient stress
Yoon, B. K., Kim, H., Oh, T. G., Oh, S. K., Jo, S., Kim, M., Chun, K.-H., Hwang, N., Lee, S., Jin, S., et al. (2023) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2217826120 · Cited by 47
Organization of Enzyme Concentration across the Metabolic Network in Cancer Cells
Madhukar, N. S., Warmoes, M. O., & Locasale, J. W. (2015) · PLoS ONE · doi:10.1371/journal.pone.0117131 · Cited by 45
Nutrients in Energy and One-Carbon Metabolism: Learning from Metformin Users
Luciano‐Mateo, F., Hernández‐Aguilera, A., Cabré, N., Camps, J., Fernández‐Arroyo, S., López‐Miranda, J., Menéndez, J. A., & Joven, J. (2017) · Nutrients · doi:10.3390/nu9020121 · Cited by 44
Quantification of lactate from various metabolic pathways and quantification issues of lactate isotopologues and isotopmers
Zhang, W., Guo, C., Jiang, K., Ying, M., & Hu, X. (2017) · Scientific Reports · doi:10.1038/s41598-017-08277-3 · Cited by 45
Reverse engineering the cancer metabolic network using flux analysis to understand drivers of human disease
Badur, M. G., & Metallo, C. M. (2017) · Metabolic Engineering · doi:10.1016/j.ymben.2017.11.013 · Cited by 44
Trojan Horse for Light-Triggered Bifurcated Production of Singlet Oxygen and Fenton-Reactive Iron within Cancer Cells
Cioloboc, D., Kennedy, C., Boice, E. N., Clark, E. R., & Kurtz, D. M. J. (2017) · Biomacromolecules · doi:10.1021/acs.biomac.7b01433 · Cited by 47
Topotecan induces apoptosis via ASCT2 mediated oxidative stress in gastric cancer
Wang, L., Liu, Y., Zhao, T., Li, Z., He, J., Zhang, B.-J., Du, H., Jiang, J., Yuan, S., & Sun, L. (2018) · Phytomedicine · doi:10.1016/j.phymed.2018.12.011 · Cited by 45
The interplay between oxidative stress and bioenergetic failure in neuropsychiatric illnesses: can we explain it and can we treat it?
Morris, G., Walder, K. R., Berk, M., Marx, W., Walker, A. J., Maes, M. H. J., & Puri, B. K. (2020) · Molecular Biology Reports · doi:10.1007/s11033-020-05590-5 · Cited by 47
Differential 3-bromopyruvate inhibition of cytosolic and mitochondrial human serine hydroxymethyltransferase isoforms, key enzymes in cancer metabolic reprogramming
Paiardini, A., Tramonti, A., Schirch, D., Guiducci, G., di Salvo, M. L., Fiascarelli, A., Giorgi, A., Maras, B., Cutruzzolà, F., & Contestabile, R. (2016) · Biochimica et Biophysica Acta (BBA) - Proteins and Proteomics · doi:10.1016/j.bbapap.2016.08.010 · Cited by 44
Toxicities of polystyrene microplastics (MPs) and hexabromocyclododecane (HBCD), alone or in combination, to the hepatopancreas of the whiteleg shrimp, Litopenaeus vannamei
Yu, Y., Hu, L., Tian, D., Yu, Y., Lu, L., Zhang, J., Huang, X., Yan, M., Chen, L., Wu, Z., et al. (2023) · Environmental Pollution · doi:10.1016/j.envpol.2023.121646 · Cited by 44
Eye on the horizon: The metabolic landscape of the RPE in aging and disease
Hansman, D., Du, J., Casson, R. J., & Peet, D. J. (2024) · Progress in Retinal and Eye Research · doi:10.1016/j.preteyeres.2024.101306 · Cited by 50
Folate can promote the methionine-dependent reprogramming of glioblastoma cells towards pluripotency
Zgheib, R., Battaglia-Hsu, S.-F., Hergalant, S., Quéré, M., Alberto, J., Chéry, C., Rouyer, P., Gauchotte, G., Guéant, J., & Namour, F. (2019) · Cell Death and Disease · doi:10.1038/s41419-019-1836-2 · Cited by 44
Quantitative analysis of glycine related metabolic pathways for one-carbon synthetic biology
Hong, Y., Ren, J., Zhang, X., Wang, W., & Zeng, A. (2019) · Current Opinion in Biotechnology · doi:10.1016/j.copbio.2019.10.001 · Cited by 44
Nanotechnology Approaches for Delivery and Targeting of Amphotericin B in Fungal and Parasitic Diseases
Jafari, M., Abolmaali, S. S., Tamaddon, A. M., Zomorodian, K., & Sarkari, B. (2021) · Nanomedicine · doi:10.2217/nnm-2020-0482 · Cited by 44
Three Classes of Antioxidant Defense Systems and the Development of Postmenopausal Osteoporosis
Yang, K., Cao, F., Xue, Y., Tao, L., & Zhu, Y. (2022) · Frontiers in Physiology · doi:10.3389/fphys.2022.840293 · Cited by 46
Analyzing Tumor Metabolism In Vivo
Faubert, B., & DeBerardinis, R. J. (2016) · Annual Review of Cancer Biology · doi:10.1146/annurev-cancerbio-050216-121954 · Cited by 44
Exploring lipid 2H/1H fractionation mechanisms in response to salinity with continuous cultures of the diatom Thalassiosira pseudonana
Maloney, A. E., Shinneman, A. L. C., Hemeon, K. M., & Sachs, J. P. (2016) · Organic Geochemistry · doi:10.1016/j.orggeochem.2016.08.015 · Cited by 43
Inhibition of DNMT1 and ERRα crosstalk suppresses breast cancer via derepression of IRF4
Vernier, M., McGuirk, S., Dufour, C. R., Wan, L., Audet‐Walsh, É., St‐Pierre, J., & Giguère, V. (2020) · Oncogene · doi:10.1038/s41388-020-01438-1 · Cited by 44
Metabolic Flux Analysis—Linking Isotope Labeling and Metabolic Fluxes
Wang, Y., Wondisford, F. E., Song, C. W., Zhang, T., & Su, X. (2020) · Metabolites · doi:10.3390/metabo10110447 · Cited by 44
Reductive stress in cancer
Zhang, L., & Tew, K. D. (2021) · Advances in cancer research · doi:10.1016/bs.acr.2021.03.009 · Cited by 43
Metabolic Determinants of Cardiomyocyte Proliferation
Mohamed, T., Abouleisa, R., & Hill, B. G. (2022) · Stem Cells · doi:10.1093/stmcls/sxac016 · Cited by 42
ALDH1L2 regulation of formate, formyl-methionine, and ROS controls cancer cell migration and metastasis
Hennequart, M., Pilley, S. E., Labuschagne, C. F., Coomes, J., Mervant, L., Driscoll, P. C., Legrave, N. M., Lee, Y., Kreuzaler, P. A., Macintyre, B., et al. (2023) · Cell Reports · doi:10.1016/j.celrep.2023.112562 · Cited by 44
Metabolism in embryonic and cancer stemness
Jang, H., Yang, J., Lee, E., & Cheong, J. (2015) · Archives of Pharmacal Research · doi:10.1007/s12272-015-0558-y · Cited by 43
Disabled cell density sensing leads to dysregulated cholesterol synthesis in glioblastoma
Kambach, D. M., Halim, A. S., Cauer, A. G., Sun, Q., Tristan, C. A., Celiku, O., Kesarwala, A. H., Shankavaram, U. T., Batchelor, E., & Stommel, J. M. (2017) · Oncotarget · doi:10.18632/oncotarget.14740 · Cited by 41
Role of coenzymes in cancer metabolism
Thapa, M., & Dallmann, G. (2019) · Seminars in Cell and Developmental Biology · doi:10.1016/j.semcdb.2019.05.027 · Cited by 45
Facile Nanolization Strategy for TherapeuticGanoderma Lucidum Spore Oilto Achieve Enhanced Protection against Radiation‐Induced Heart Disease
Dai, C., He, L., Ma, B., & Chen, T. (2019) · Small · doi:10.1002/smll.201902642 · Cited by 44
Transfer of glucose hydrogens via acetyl-CoA, malonyl-CoA, and NADPH to fatty acids during de novo lipogenesis
Belew, G. D., Silva, J., Rito, J., Tavares, L. C., Viegas, I., Teixeira, J., Oliveira, P. J., Macedo, M. P., & Jones, J. G. (2019) · Journal of Lipid Research · doi:10.1194/jlr.ra119000354 · Cited by 42
Linkage between Carbon Metabolism, Redox Status and Cellular Physiology in the Yeast Saccharomyces cerevisiae Devoid of SOD1 or SOD2 Gene
Maślanka, R., Zadrąg‐Tęcza, R., & Kwolek‐Mirek, M. (2020) · Genes · doi:10.3390/genes11070780 · Cited by 42
Arginine methylation of MTHFD1 by PRMT5 enhances anoikis resistance and cancer metastasis
Meng, Q., Lu, Y., Chen, W., Wang, Z., Lin, J., Liao, K. L., Luo, X.-J., Yu, K., Han, Y., Li, J., et al. (2022) · Oncogene · doi:10.1038/s41388-022-02387-7 · Cited by 41
Oncogenes strike a balance between cellular growth and homeostasis
Qiu, B., & Simon, M. C. (2015) · Seminars in Cell and Developmental Biology · doi:10.1016/j.semcdb.2015.08.005 · Cited by 44
Hyperglycemia-induced metabolic compensation inhibits metformin sensitivity in ovarian cancer
Litchfield, L. M., Mukherjee, A., Eckert, M. A., Johnson, A., Mills, K. A., Pan, S., Shridhar, V., Lengyel, E. R., & Romero, I. L. (2015) · Oncotarget · doi:10.18632/oncotarget.4556 · Cited by 44
Cytosolic aconitase activity sustains adipogenic capacity of adipose tissue connecting iron metabolism and adipogenesis
Moreno, M., Ortega, F. J., Xifra, G., Ricart, W., Fernández‐Real, J. M., & Moreno‐Navarrete, J. M. (2014) · The FASEB Journal · doi:10.1096/fj.14-258996 · Cited by 41
One-Carbon Metabolic Pathway Rewiring in Escherichia coli Reveals an Evolutionary Advantage of 10-Formyltetrahydrofolate Synthetase (Fhs) in Survival under Hypoxia
Sah, S., Aluri, S., Rex, K., & Varshney, U. (2014) · Journal of Bacteriology · doi:10.1128/jb.02365-14 · Cited by 41
Metabolic Reprogramming by Folate Restriction Leads to a Less Aggressive Cancer Phenotype
Ashkavand, Z., O’Flanagan, C. H., Hennig, M., Du, X., Hursting, S. D., & Krupenko, S. A. (2017) · Molecular Cancer Research · doi:10.1158/1541-7786.mcr-16-0317 · Cited by 41
Histidine-Dependent Protein Methylation Is Required for Compartmentalization of CTP Synthase
Lin, W.-C., Chakraborty, A., Huang, S., Wang, P., Hsieh, Y., Chien, K., Lee, Y., Chang, C., Tang, H.-Y., Lin, Y.-T., et al. (2018) · Cell Reports · doi:10.1016/j.celrep.2018.08.007 · Cited by 41
6-Phosphofructo-2-Kinase/Fructose-2,6-Biphosphatase-2 Regulates TP53-Dependent Paclitaxel Sensitivity in Ovarian and Breast Cancers
Yang, H., Zhang, S., Jiang, Y., Mao, W., Pang, L., Redwood, A. B., Jeter-Jones, S. L., Jennings, N. B., Ornelas, A., Zhou, J., et al. (2019) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-18-3448 · Cited by 41
The TIM22 complex mediates the import of sideroflexins and is required for efficient mitochondrial one-carbon metabolism
Jackson, T. D., Hock, D. H., Fujihara, K. M., Palmer, C. S., Frazier, A. E., Low, Y. C., Kang, Y., Ang, C., Clemons, N. J., Thorburn, D. R., et al. (2021) · Molecular Biology of the Cell · doi:10.1091/mbc.e20-06-0390 · Cited by 42
Mammalian Mitochondrial and Cytosolic Folylpolyglutamate Synthetase Maintain the Subcellular Compartmentalization of Folates
Lawrence, S. A., Titus, S. A., Ferguson, J., Heineman, A., Taylor, S. M., & Moran, R. G. (2014) · Journal of Biological Chemistry · doi:10.1074/jbc.m114.593244 · Cited by 40
Mathematical models of cancer metabolism
Markert, E. K., & Vázquez, A. (2015) · Cancer & Metabolism · doi:10.1186/s40170-015-0140-6 · Cited by 41
Chasing One-Carbon Units to Understand the Role of Serine in Epigenetics
Parker, S. J., & Metallo, C. M. (2016) · Molecular Cell · doi:10.1016/j.molcel.2016.01.006 · Cited by 40
MicroRNA-mediated regulation of glutathione and methionine metabolism and its relevance for liver disease
Lu, S. C.-L., Mato, J. M., Espinosa‐Díez, C., & Lamas, S. (2016) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2016.03.021 · Cited by 40
Alteration of cellular metabolism in cancer cells and its therapeutic prospects
Biswal, B. N., Das, S., Das, B., & Rath, R. (2017) · Journal of Oral and Maxillofacial Pathology · doi:10.4103/jomfp.jomfp_60_17 · Cited by 42
Metabolic reprogramming and redox adaptation in sorafenib‐resistant leukemia cells: detected by untargeted metabolomics and stable isotope tracing analysis
You, X., Jiang, W., Lu, W., Zhang, H., Yu, T., Tian, J., Wen, S., Garcia‐Manero, G., Huang, P., & Hu, Y. (2019) · 癌症：英文版 · doi:10.1186/s40880-019-0362-z · Cited by 40
How DNA methylation affects the Warburg effect
Zhu, X., Xuan, Z., Chen, J., Li, Z., Zheng, S., & Song, P. (2020) · International Journal of Biological Sciences · doi:10.7150/ijbs.45420 · Cited by 42
Cytosolic ME1 integrated with mitochondrial IDH2 supports tumor growth and metastasis
Shao, C., Lu, W., Du, Y., Yan, W., Bao, Q., Tian, Y., Wang, G., Ye, H., & Hao, H. (2020) · Redox Biology · doi:10.1016/j.redox.2020.101685 · Cited by 41
Defining the ATPome reveals cross-optimization of metabolic pathways
Bennett, N. K., Nguyen, M. K., Darch, M. A., Nakaoka, H. J., Cousineau, D., ten Hoeve, J., Graeber, T. G., Schuelke, M., Maltepe, E., Kampmann, M., et al. (2020) · Nature Communications · doi:10.1038/s41467-020-18084-6 · Cited by 40
Mechanisms Governing Metabolic Heterogeneity in Breast Cancer and Other Tumors
Patra, S., Elahi, N., Armorer, A., Arunachalam, S., Omala, J., Hamid, I., Ashton, A. W., Joyce, D. A., Jiao, X., & Pestell, R. G. (2021) · Frontiers in Oncology · doi:10.3389/fonc.2021.700629 · Cited by 43
Specific circulating phospholipids, acylcarnitines, amino acids and biogenic amines are aerobic exercise markers
Felder, T. K., Ring‐Dimitriou, S., Auer, S., Soyal, S. M., Kedenko, L., Rinnerthaler, M., Cadamuro, J., Haschke‐Becher, E., Aigner, E. S., Paulweber, B., et al. (2017) · Journal of science and medicine in sport · doi:10.1016/j.jsams.2016.11.011 · Cited by 41
NADPH Oxidases in the Central Nervous System: Regional and Cellular Localization and the Possible Link to Brain Diseases
Fang, J., Sheng, R., & Qin, Z. (2021) · Antioxidants and Redox Signaling · doi:10.1089/ars.2021.0040 · Cited by 41
Mitochondrial Redox Metabolism: The Epicenter of Metabolism during Cancer Progression
Choudhury, F. K. (2021) · Antioxidants · doi:10.3390/antiox10111838 · Cited by 44
Targeting allosteric regulation of cancer metabolism
Kremer, D. M., & Lyssiotis, C. A. (2022) · Nature Chemical Biology · doi:10.1038/s41589-022-00997-6 · Cited by 43
Metabolic flexibilities and vulnerabilities in the pentose phosphate pathway of the zoonotic pathogen Toxoplasma gondii
Xia, N., Guo, X., Guo, Q., Gupta, N., Ji, N., Shen, B., Xiao, L., & Feng, Y. (2022) · PLoS Pathogens · doi:10.1371/journal.ppat.1010864 · Cited by 40
NERNST: a genetically-encoded ratiometric non-destructive sensing tool to estimate NADP(H) redox status in bacterial, plant and animal systems
Molinari, P. E., Krapp, A. R., Weiner, A. M. J., Beyer, H. M., Kondadi, A. K., Blomeier, T., López, M., Bustos‐Sanmamed, P., Tevere, E., Weber, W., et al. (2023) · Nature Communications · doi:10.1038/s41467-023-38739-4 · Cited by 38
PKM2 functions as a histidine kinase to phosphorylate PGAM1 and increase glycolysis shunts in cancer
Wang, Y., Shu, H., Qu, Y., Jin, X., Liu, J., Peng, W., Wang, L., Hao, M., Xia, M., Zhao, Z., et al. (2024) · The EMBO Journal · doi:10.1038/s44318-024-00110-8 · Cited by 43
MicroRNA-940 inhibits glioma progression by blocking mitochondrial folate metabolism through targeting of MTHFD2.
Xu, T., Zhang, K., Shi, J., Huang, B., Wang, X., Qian, K., Ma, T., Qian, T., Song, Z., & Li, L. (2019) · Europe PMC (PubMed Central) · Cited by 39
Aldh1l2 knockout mouse metabolomics links the loss of the mitochondrial folate enzyme to deregulation of a lipid metabolism observed in rare human disorder
Krupenko, N. I., Sharma, J., Pediaditakis, P., Helke, K. L., Hall, M. S., Du, X., Sumner, S., & Krupenko, S. A. (2020) · Human Genomics · doi:10.1186/s40246-020-00291-3 · Cited by 39
Metabolic modeling of host–microbe interactions for therapeutics in colorectal cancer
Bhalla, P., Rengaswamy, R., Karunagaran, D., Suraishkumar, G. K., & Sahoo, S. (2022) · npj Systems Biology and Applications · doi:10.1038/s41540-021-00210-9 · Cited by 41
YAP/TAZ-mediated activation of serine metabolism and methylation regulation is critical for LKB1-deficient breast cancer progression
Wu, Q., Li, J., Sun, S., Chen, X., Zhang, H., Li, B., & Sun, S. (2017) · Bioscience Reports · doi:10.1042/bsr20171072 · Cited by 38
Simultaneous measurement of folate cycle intermediates in different biological matrices using liquid chromatography–tandem mass spectrometry
Nandania, J., Kokkonen, M. K., Euro, L., & Velagapudi, V. (2018) · Journal of Chromatography B · doi:10.1016/j.jchromb.2018.06.008 · Cited by 38
Reductive Stress, Bioactive Compounds, Redox-Active Metals, and Dormant Tumor Cell Biology to Develop Redox-Based Tools for the Treatment of Cancer
Quiles, J. L., Sánchez‐González, C., Ramírez, L. V., Giampieri, F., Navarro‐Hortal, M. D., Xiao, J., Llopis, J., Battino, M. A., & Varela‐López, A. (2020) · Antioxidants and Redox Signaling · doi:10.1089/ars.2020.8051 · Cited by 39
Discovering How Heme Controls Genome Function Through Heme-omics
Liao, R., Zheng, Y., Liu, X., Zhang, Y., Seim, G. L., Tanimura, N., Wilson, G. M., Hematti, P., Coon, J. J., Fan, J., et al. (2020) · Cell Reports · doi:10.1016/j.celrep.2020.107832 · Cited by 35
Self-citation
Allosteric inhibition of MTHFR prevents futile SAM cycling and maintains nucleotide pools in one-carbon metabolism
Bhatia, M., Thakur, J., Suyal, S., O’Niel, R. A., Chakraborty, R., Pradhan, S., Sharma, M., Sengupta, S., Laxman, S., Masakapalli, S. K., et al. (2020) · Journal of Biological Chemistry · doi:10.1074/jbc.ra120.015129 · Cited by 38
Role of Vitamin B12 and Folate in Metabolic Syndrome
Ashok, T., Puttam, H., Tarnate, V. C. A., Jhaveri, S., Avanthika, C., Treviño, A. G. T., Sandeep, S. L., & Ahmed, N. (2021) · Cureus · doi:10.7759/cureus.18521 · Cited by 43
Quantitative modeling of pentose phosphate pathway response to oxidative stress reveals a cooperative regulatory strategy
Hurbain, J., Thommen, Q., Anquez, F., & Pfeuty, B. (2022) · iScience · doi:10.1016/j.isci.2022.104681 · Cited by 42
Target enzymes in serine‐glycine‐one‐carbon metabolic pathway for cancer therapy
Sun, W. Y., Zhao, E., & Cui, H. (2022) · International Journal of Cancer · doi:10.1002/ijc.34353 · Cited by 39
PI3Kγ maintains the self-renewal of acute myeloid leukemia stem cells by regulating the pentose phosphate pathway
Gu, H., Chen, C., Hou, Z.-S., He, X., Xie, S., Ni, J., Qian, C., Cheng, X., Jiang, T., Yang, C., et al. (2024) · Blood · doi:10.1182/blood.2023022202 · Cited by 39
Metabolic regulation by p53: Implications for cancer therapy
Koo, K. Y., Moon, K., He, S., & Lee, M.-S. (2025) · Molecules and Cells · doi:10.1016/j.mocell.2025.100198 · Cited by 45
Mitochondrial NADPH fuels mitochondrial fatty acid synthesis and lipoylation to power oxidative metabolism
Kim, D., Kesavan, R., Ryu, K., Dey, T., Marckx, A. T., Menezes, C. J., Praharaj, P. P., Morley, S. A., Ko, B., Soflaee, M. H., et al. (2025) · Nature Cell Biology · doi:10.1038/s41556-025-01655-4 · Cited by 40
Localization of NADPH Production: A Wheel within a Wheel
Maddocks, O. D. K., Labuschagne, C. F., & Vousden, K. H. (2014) · Molecular Cell · doi:10.1016/j.molcel.2014.07.001 · Cited by 36
Benzo[a]pyrene-induced metabolic shift from glycolysis to pentose phosphate pathway in the human bladder cancer cell line RT4
Verma, N., Pink, M., Boland, S., Rettenmeier, A. W., & Schmitz‐Spanke, S. (2017) · Scientific Reports · doi:10.1038/s41598-017-09936-1 · Cited by 37
The Effects of PPAR Stimulation on Cardiac Metabolic Pathways in Barth Syndrome Mice
Schafer, C., Moore, V., Dasgupta, N., Javadov, S. A., James, J. F., Glukhov, A. I., Strauss, A. W., & Khuchua, Z. A. (2018) · Frontiers in Pharmacology · doi:10.3389/fphar.2018.00318 · Cited by 37
Human Cytosolic and Mitochondrial Serine Hydroxymethyltransferase Isoforms in Comparison: Full Kinetic Characterization and Substrate Inhibition Properties
Tramonti, A., Nardella, C., di Salvo, M. L., Barile, A., Cutruzzolà, F., & Contestabile, R. (2018) · Biochemistry · doi:10.1021/acs.biochem.8b01074 · Cited by 37
Snail augments fatty acid oxidation by suppression of mitochondrial ACC2 during cancer progression
Yang, J. H., Kim, N. H., Yun, J. S., Cho, E. S., Cha, Y. H., Cho, S. B., Lee, S.-H., Cha, S. Y., Kim, S., Choi, J., et al. (2020) · Life Science Alliance · doi:10.26508/lsa.202000683 · Cited by 37
Glucose Protects Cochlear Hair Cells Against Oxidative Stress and Attenuates Noise-Induced Hearing Loss in Mice
Xiong, H., Lai, L., Ye, Y., & Zheng, Y. (2021) · Neuroscience Bulletin · doi:10.1007/s12264-020-00624-1 · Cited by 38
Targeting of chimeric antigen receptor T cell metabolism to improve therapeutic outcomes
Nanjireddy, P., Olejniczak, S. H., & Buxbaum, N. P. (2023) · Frontiers in Immunology · doi:10.3389/fimmu.2023.1121565 · Cited by 39
The airway epithelium undergoes metabolic reprogramming in individuals at high risk for lung cancer
Rahman, S. M. J., Ji, X., Zimmerman, L. J., Li, M., Harris, B. K., Hoeksema, M. D., Trenary, I. A., Zou, Y., Qian, J., Slebos, R. J. C., et al. (2016) · JCI Insight · doi:10.1172/jci.insight.88814 · Cited by 37
Biomedical applications of cell- and tissue-specific metabolic network models
Fouladiha, H., & Marashi, S. (2017) · Journal of Biomedical Informatics · doi:10.1016/j.jbi.2017.02.014 · Cited by 37
T-protein is present in large excess over the other proteins of the glycine cleavage system in leaves of Arabidopsis
Timm, S., Giese, J., Engel, N., Wittmiß, M., Florian, A., Fernie, A. R., & Bauwe, H. (2017) · Planta · doi:10.1007/s00425-017-2767-8 · Cited by 36
Metabolic collateral lethal target identification reveals MTHFD2 paralogue dependency in ovarian cancer
Achreja, A., Yu, T., Mittal, A., Choppara, S., Animasahun, O. H., Nenwani, M., Wuchu, F., Meurs, N., Mohan, A., Jeon, J. H., et al. (2022) · Nature Metabolism · doi:10.1038/s42255-022-00636-3 · Cited by 33
Formate metabolism in fetal and neonatal sheep
Washburn, S. E., Caudill, M. A., Malysheva, O., MacFarlane, A. J., Behan, N. A., Harnett, B., MacMillan, L., Pongnopparat, T., Brosnan, J. T., & Brosnan, M. E. (2015) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00046.2015 · Cited by 36
Redox regulation of chromatin remodelling in plants
Plšková, Z., Breusegem, F. V., & Kerchev, P. (2024) · Plant Cell & Environment · doi:10.1111/pce.14843 · Cited by 35
Vitamin C Activates the Folate-Mediated One-Carbon Cycle in C2C12 Myoblasts
Magaña, A. A., Reed, R. L., Koluda, R., Miranda, C. L., Maier, C. S., & Stevens, J. F. (2020) · Antioxidants · doi:10.3390/antiox9030217 · Cited by 34
Mechanisms of Congenital Malformations in Pregnancies with Pre-existing Diabetes
Loeken, M. R. (2020) · Current Diabetes Reports · doi:10.1007/s11892-020-01338-4 · Cited by 43
Glycolate combats massive oxidative stress by restoring redox potential in Caenorhabditis elegans
Diez, V., Traikov, S., Schmeißer, K., Adhikari, A. K. D., & Kurzchalia, T. V. (2021) · Communications Biology · doi:10.1038/s42003-021-01669-2 · Cited by 34
Analysis of Factors Affecting 5-ALA Fluorescence Intensity in Visualizing Glial Tumor Cells—Literature Review
Mazurek, M., Szczepanek, D., Orzyłowska, A., & Rola, R. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms23020926 · Cited by 38
Identification of Fumarate Hydratase Inhibitors with Nutrient-Dependent Cytotoxicity
Takeuchi, T., Schumacker, P. T., & Kozmin, S. A. (2014) · Journal of the American Chemical Society · doi:10.1021/ja5101257 · Cited by 34
Interplay between cytosolic disulfide reductase systems and the Nrf2/Keap1 pathway
Schmidt, E. E. (2015) · Biochemical Society Transactions · doi:10.1042/bst20150021 · Cited by 35
Editor’s Highlight: A Genome-wide Screening of Target Genes Against Silver Nanoparticles in Fission Yeast
Lee, A., Lee, S.-J., Lee, M., Nam, M., Lee, S., Choi, J., Lee, H.-J., Kim, D.-U., & Hoe, K. (2017) · Toxicological Sciences · doi:10.1093/toxsci/kfx208 · Cited by 34
Analytical Methods for Mass Spectrometry-Based Metabolomics Studies
Wang, S., Blair, I. A., & Mesaros, C. (2019) · Advances in experimental medicine and biology · doi:10.1007/978-3-030-15950-4_38 · Cited by 35
Potassium and Sodium Channels and the Warburg Effect: Biophysical Regulation of Cancer Metabolism
Iorio, J., Petroni, G., Duranti, C., & Lastraioli, E. (2019) · Bioelectricity · doi:10.1089/bioe.2019.0017 · Cited by 33
Metabolic therapy and bioenergetic analysis: The missing piece of the puzzle
Duraj, T., Carrión-Navarro, J., Seyfried, T. N., Garcia‐Romero, N., & Ayuso‐Sacido, Á. (2021) · Molecular Metabolism · doi:10.1016/j.molmet.2021.101389 · Cited by 36
Nitric oxide protects against cochlear hair cell damage and noise-induced hearing loss through glucose metabolic reprogramming
Yang, H., Zhu, Y., Ye, Y., Guan, J., Min, X., & Xiong, H. (2021) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2021.11.020 · Cited by 34
Endogenous cross-talk of fungal metabolites
Sheridan, K. J., Dolan, S. K., & Doyle, S. (2015) · Frontiers in Microbiology · doi:10.3389/fmicb.2014.00732 · Cited by 37
Dual pharmacological inhibition of glutathione and thioredoxin systems synergizes to kill colorectal carcinoma stem cells
Tanaka, G., Inoue, K.-I., Shimizu, T., Akimoto, K., & Kubota, K. (2016) · Cancer Medicine · doi:10.1002/cam4.844 · Cited by 34
Monitoring NAD(H) and NADP(H) dynamics during organismal development with genetically encoded fluorescent biosensors
Li, T., Zou, Y., Liu, S., Yang, Y. A., Zhang, Z., & Zhao, Y. (2022) · Cell Regeneration · doi:10.1186/s13619-021-00105-4 · Cited by 35
Strategies for Extending Metabolomics Studies with Stable Isotope Labelling and Fluxomics
Srivastava, A., Kowalski, G. M., Callahan, D. L., Meikle, P. J., & Creek, D. J. (2016) · Metabolites · doi:10.3390/metabo6040032 · Cited by 33
Alterations in cellular metabolism triggered by URA7 or GLN3 inactivation cause imbalanced dNTP pools and increased mutagenesis
Schmidt, T. T., Reyes, G. X., Gries, K., Ceylan, C. Ü., Sharma, S., Meurer, M., Knop, M., Chabes, A., & Hombauer, H. (2017) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1618714114 · Cited by 33

Authors: Fan, J., Ye, J., Kamphorst, J. J., Shlomi, T., Thompson, C. B., & Rabinowitz, J. D.
Affiliations: Princeton University (US)
Memorial Sloan Kettering Cancer Center (US)
Technion – Israel Institute of Technology (IL)
Corresponding author: Rabinowitz, Joshua D.
ORCID: Fan, Jing
Ye, Jiangbin
Kamphorst, Jurre J.
Shlomi, Tomer
Thompson, Craig B.
Rabinowitz, Joshua D.
Venue: Nature
Publisher: Springer Science and Business Media LLC
Published: 2014-05-04
Volume: 510
Issue: 7504
Pages: 298-302
ISSN: 0028-0836 (ISSN-L)
1476-4687
DOI: 10.1038/nature13236
PMC: PMC4104482
OpenAlex: W2017035524
Cited by: 1,114
References: 41
Citations by year: 2026: 65 · 2025: 90 · 2024: 91 · 2023: 79 · 2022: 87 · 2021: 116 · 2020: 109 · 2019: 102 · 2018: 65 · 2017: 106 · 2016: 98 · 2015: 74 · 2014: 31
FWCI: 86.15
Type: journal article
Language: en
Update notices: erratum (2014-09-24)
Open access: green
www.ncbi.nlm.nih.gov
Licence: www.springer.com/tdm (tdm)
www.springer.com/tdm (vor)
Locations: Nature (publishedVersion)
PubMed (publishedVersion)
PubMed Central (acceptedVersion)
RePEc: Research Papers in Economics (submittedVersion)
ENLIGHTEN (Jurnal Bimbingan dan Konseling Islam) (submittedVersion)
Funders: Howard Hughes Medical Institute
Memorial Sloan-Kettering Cancer Center
National Institutes of Health
National Cancer Institute (P01CA104838, R01CA105463, P30CA072720, R01CA163591)
National Institute of General Medical Sciences (P50GM071508)
National Institute of Allergy and Infectious Diseases (R01AI097382)
Topics: Health Sciences › Nursing › Nutrition and Dietetics › Folate and B Vitamins Research
Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Hypoxia, and Metabolism
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Biochemical and Molecular Research
Keywords: NADPH production, folate metabolism, methylenetetrahydrofolate dehydrogenase, oxidative pentose phosphate pathway, one-carbon metabolism, serine metabolism, glycine metabolism, deuterium labeling, carbon labeling
MeSH terms: Animals, Carbon, Cell Line, Leucovorin, Cytosol, Folic Acid, Glutathione, Glycine, Humans, Isoenzymes, Methylenetetrahydrofolate Dehydrogenase (NADP), Mitochondria, NADP, Oxidation-Reduction, Pentose Phosphate Pathway, Serine, Tetrahydrofolates, Oxidative Stress, Cell Line, Tumor, Mice, HEK293 Cells

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review

Quantitative flux analysis reveals folate-dependent NADPH production

Abstract

Overview

Integrity signals

Verification

Claims the paper makes

Claims other papers make about this one

Self-check

Citations

Cites

Cited by

Related

Metadata

Record

About these checks