
Hosios, A. M. et al. Amino acids moderately than glucose account for almost all of cell mass in proliferating mammalian cells. Dev. Cell 36, 540–549 (2016).
Google Scholar
Yao, C.-H. et al. Exogenous fatty acids are the popular supply of membrane lipids in proliferating fibroblasts. Cell Chem. Biol. 23, 483–493 (2016).
Google Scholar
Jain, M. et al. Metabolite profiling identifies a key position for glycine in fast most cancers cell proliferation. Science 336, 1040 (2012).
Google Scholar
Damaraju, V. L. et al. Nucleoside anticancer medicine: the position of nucleoside transporters in resistance to most cancers chemotherapy. Oncogene 22, 7524–7536 (2003).
Google Scholar
Muir, A., Danai, L. V. & Vander Heiden, M. G. Microenvironmental regulation of most cancers cell metabolism: implications for experimental design and translational research. Dis. Fashions Mech. 11, dmm035758–12 (2018).
Sullivan, M. R. et al. Quantification of microenvironmental metabolites in murine cancers reveals determinants of tumor nutrient availability. Elife 8, e44235 (2019).
Google Scholar
Vaupel, P., Kallinowski, F. & Okunieff, P. Blood stream, oxygen and nutrient provide, and metabolic microenvironment of human tumors: a overview. Most cancers Res. 49, 6449 (1989).
Google Scholar
Eales, Okay. L., Hollinshead, Okay. E. R. & Tennant, D. A. Hypoxia and metabolic adaptation of most cancers cells. Oncogenesis 5, e190–8 (2016).
Google Scholar
Hu, J. et al. Heterogeneity of tumor-induced gene expression modifications within the human metabolic community. Nat. Biotechnol. 31, 522–529 (2013).
Google Scholar
Gui, D. Y. et al. Atmosphere dictates dependence on mitochondrial advanced I for NAD+ and aspartate Manufacturing and determines most cancers cell sensitivity to metformin. Cell Metab. 24, 716–727 (2016).
Google Scholar
Sullivan, L. B. et al. Supporting aspartate biosynthesis is a vital perform of respiration in proliferating cells. Cell 162, 552–563 (2015).
Google Scholar
Sullivan, L. B. et al. Aspartate is an endogenous metabolic limitation for tumour progress. Nat. Cell Biol. 20, 1–12 (2018).
Birsoy, Okay. et al. A vital position of the mitochondrial electron transport chain in cell proliferation is to allow aspartate synthesis. Cell 162, 540–551 (2015).
Google Scholar
Garcia-Bermudez, J. et al. Aspartate is a limiting metabolite for most cancers cell proliferation beneath hypoxia and in tumours. Nat. Cell Biol. 20, 1–12 (2018).
Fernandez-de-Cossio-Diaz, J. & Vazquez, A. Limits of cardio metabolism in most cancers cells. Sci. Rep. 7, 13488 (2017).
Google Scholar
Titov, D. V. et al. Complementation of mitochondrial electron transport chain by manipulation of the NAD+/NADH ratio. Science 352, 231–235 (2016).
Google Scholar
Diehl, F. F., Lewis, C. A., Fiske, B. P. & Vander Heiden, M. G. Mobile redox state constrains serine synthesis and nucleotide manufacturing to influence cell proliferation. Nat. Metab. 1, 861–867 (2019).
Bao, X. R. et al. Mitochondrial dysfunction remodels one-carbon metabolism in human cells. Elife 5, e10575 (2016).
Google Scholar
Murphy, J. P. et al. The NAD+ salvage pathway helps PHGDH-driven serine biosynthesis. Cell Rep. 24, 2381–2391 (2018).
Google Scholar
Kim, W. et al. Polyunsaturated fatty acid desaturation is a mechanism for glycolytic NAD+ recycling. Cell Metab. 1–42 (2019).
Worth, N. C. & Stevens, L. Fundamentals of Enzymology (Oxford College Press, 2000).
Los, D. A. & Murata, N. Construction and expression of fatty acid desaturases. Biochim. Biophys. Acta 1394, 3–15 (1998).
Google Scholar
Park, S. H. et al. Phosphorylation-activity relationships of AMPK and acetyl-CoA carboxylase in muscle. J. Appl. Physiol. 92, 2475–2482 (2002).
Google Scholar
Schulz, H. Beta oxidation of fatty acids. Biochim. Biophys. Acta 1081, 109–120 (1991).
Google Scholar
Kamphorst, J. J. et al. Hypoxic and Ras-transformed cells assist progress by scavenging unsaturated fatty acids from lysophospholipids. Proc. Natl Acad. Sci. USA 110, 8882 (2013).
Google Scholar
Ackerman, D. et al. Triglycerides promote lipid homeostasis throughout hypoxic stress by balancing fatty acid saturation. Cell Rep. 24, 2596–2605 (2018).
Google Scholar
Bensaad, Okay. et al. Fatty acid uptake and lipid storage induced by HIF-1α contribute to cell progress and survival after hypoxia-reoxygenation. Cell Rep. 9, 349–365 (2014).
Google Scholar
Jain, I. H. et al. Genetic display for cell health in excessive or low oxygen highlights mitochondrial and lipid metabolism. Cell 181, 716–727 (2020).
Google Scholar
Luengo, A. et al. Elevated demand for NAD+ relative to ATP drives cardio glycolysis. Mol. Cell 81, 691–707 (2021).
Google Scholar
Harris, A. L. Hypoxia—a key regulatory think about tumour progress. Nat. Rev. Most cancers 2, 38–47 (2002).
Google Scholar
Clever, D. R. et al. Hypoxia promotes isocitrate dehydrogenase-dependent carboxylation of α-ketoglutarate to citrate to assist cell progress and viability. Proc. Natl Acad. Sci. USA 108, 19611–19616 (2011).
Google Scholar
Metallo, C. M. et al. Reductive glutamine metabolism by IDH1 mediates lipogenesis beneath hypoxia. Nature 481, 380–384 (2012).
Google Scholar
Mullen, A. R. et al. Reductive carboxylation helps progress in tumour cells with faulty mitochondria. Nature 481, 385–388 (2011).
Google Scholar
Dupuy, F. et al. PDK1-dependent metabolic reprogramming dictates metastatic potential in breast most cancers. Cell Metab. 22, 577–589 (2015).
Google Scholar
Duarte, N. C. et al. World reconstruction of the human metabolic community based mostly on genomic and bibliomic knowledge. Proc. Natl Acad. Sci. USA 104, 1777–1782 (2007).
Google Scholar
Orth, J. D., Thiele, I. & Palsson, B. Ø. What’s flux stability evaluation? Nat. Biotechnol. 28, 245–248 (2010).
Google Scholar
Jerby, L., Shlomi, T. & Ruppin, E. Computational reconstruction of tissue‐particular metabolic fashions: utility to human liver metabolism. Mol. Syst. Biol. 6, 401 (2010).
Google Scholar
Zielinski, D. C. et al. Programs biology evaluation of drivers underlying hallmarks of most cancers cell metabolism. Sci. Rep. 7, 41241 (2017).
Google Scholar
Saggerson, E. D. The regulation of glyceride synthesis in remoted white-fat cells. The consequences of acetate, pyruvate, lactate, palmitate, electron-acceptors, uncoupling brokers and oligomycin. Biochem. J. 128, 1069–1078 (1972).
Google Scholar
Clever, E. M. Jr & Ball, E. G. Malic enzyme and lipogenesis. Proc. Natl Acad. Sci. USA 52, 1255–1263 (1964).
Google Scholar
Liu, L. et al. Malic enzyme tracers reveal hypoxia-induced swap in adipocyte NADPH pathway utilization. Nat. Chem. Biol. 12, 345–352 (2016).
Google Scholar
Hosios, A. M. & Vander Heiden, M. G. The redox necessities of proliferating mammalian cells. J. Biol. Chem. 293, 7490–7498 (2018).
Google Scholar
DeBerardinis, R. J. et al. Past cardio glycolysis: remodeled cells can interact in glutamine metabolism that exceeds the requirement for protein and nucleotide synthesis. Proc. Natl Acad. Sci. USA 104, 19345 (2007).
Google Scholar
Santos, C. R. & Schulze, A. Lipid metabolism in most cancers. FEBS J. 279, 2610–2623 (2012).
Google Scholar
Hosios, A., Li, Z., Lien, E. & Vander Heiden, M. Preparation of lipid-stripped serum for the research of lipid metabolism in cell tradition. Bio. Protoc. 8, e2876 (2018).
Google Scholar
Gameiro, P. A. et al. In vivo HIF-mediated reductive carboxylation is regulated by citrate ranges and sensitizes VHL-deficient cells to glutamine deprivation. Cell Metab. 17, 372–385 (2013).
Google Scholar
Kaplon, J. et al. A key position for mitochondrial gatekeeper pyruvate dehydrogenase in oncogene-induced senescence. Nature 498, 109–112 (2013).
Google Scholar
Linn, T. C., Pettit, F. H. & Reed, L. J. α-keto acid dehydrogenase complexes, X. Regulation of the exercise of pyruvate dehydrogenase advanced from beef kidney mitochondria by phosphorylation and dephosphorylation. Proc. Natl Acad. Sci. USA 62, 234–241 (1969).
Google Scholar
Schell, J. C. et al. A task for the mitochondrial pyruvate provider as a repressor of the Warburg impact and colon most cancers cell progress. Mol. Cell 56, 400–413 (2014).
Google Scholar
Vacanti, N. M. et al. Regulation of substrate utilization by the mitochondrial pyruvate provider. Mol. Cell 56, 425–435 (2014).
Google Scholar
Yang, C. et al. Glutamine oxidation maintains the TCA cycle and cell survival throughout impaired mitochondrial pyruvate transport. Mol. Cell 56, 414–424 (2014).
Google Scholar
Bricker, D. Okay. et al. A mitochondrial pyruvate provider required for pyruvate uptake in yeast, Drosophila and people. Science 337, 96–100 (2012).
Google Scholar
Herzig, S. et al. Identification and practical expression of the mitochondrial pyruvate provider. Science 337, 93–96 (2012).
Fendt, S.-M. et al. Reductive glutamine metabolism is a perform of the α-ketoglutarate-to-citrate ratio in cells. Nat. Commun. 4, 2236 (2013).
Google Scholar
Owen, M. R., Doran, E. & Halestrap, A. P. Proof that metformin exerts its anti-diabetic results via inhibition of advanced 1 of the mitochondrial respiratory chain. Biochem. J. 348, 607–614 (2000).
Google Scholar
Bücher, T. et al. State of oxidation–discount and state of binding within the cytosolic NADH-system as disclosed by equilibration with extracellular lactate/pyruvate in hemoglobin-free perfused rat liver. Eur. J. Biochem. 27, 301–317 (1972).
Google Scholar
Hung, Y. P., Albeck, J. G., Tantama, M. & Yellen, G. Imaging cytosolic NADH–NAD+ redox state with a genetically encoded fluorescent biosensor. Cell Metab. 14, 545–554 (2011).
Google Scholar
Hatzivassiliou, G. et al. ATP citrate lyase inhibition can suppress tumor cell progress. Most cancers Cell 8, 311–321 (2005).
Google Scholar
Faubert, B. et al. Lactate metabolism in human lung tumors. Cell 171, 358–371 (2017).
Google Scholar
Hui, S. et al. Glucose feeds the TCA cycle through circulating lactate. Nature 551, 115–118 (2017).
Google Scholar
Zhao, Y. et al. In vivo monitoring of mobile power metabolism utilizing SoNar, a extremely responsive sensor for NAD+/NADH redox state. Nat. Protoc. 11, 1345–1359 (2016).
Google Scholar
Garcia, D. & Shaw, R. J. AMPK: mechanisms of mobile power sensing and restoration of metabolic stability. Mol. Cell 66, 789–800 (2017).
Google Scholar
Latasa, M. J., Moon, Y. S., Kim, Okay. H. & Sul, H. S. Dietary regulation of the fatty acid synthase promoter in vivo: sterol regulatory factor binding protein features via an upstream area containing a sterol regulatory factor. Proc. Natl Acad. Sci. USA 97, 10619–10624 (2000).
Google Scholar
Lewis, C. A. et al. SREBP maintains lipid biosynthesis and viability of most cancers cells beneath lipid- and oxygen-deprived situations and defines a gene signature related to poor survival in glioblastoma multiforme. Oncogene 34, 5128–5140 (2015).
Comerford, S. A. et al. Acetate dependence of tumors. Cell 159, 1591–1602 (2014).
Google Scholar
Mashimo, T. et al. Acetate Is a bioenergetic substrate for human glioblastoma and mind metastases. Cell 159, 1603–1614 (2014).
Google Scholar
Schug, Z. T. et al. Acetyl-CoA synthetase 2 promotes acetate utilization and maintains most cancers cell progress beneath metabolic stress. Most cancers Cell 27, 57–71 (2015).
Google Scholar
Bulusu, V. et al. Acetate recapturing by nuclear acetyl-CoA synthetase 2 prevents lack of histone acetylation throughout oxygen and serum limitation. Cell Rep. 18, 647–658 (2017).
Google Scholar
Liu, X. et al. Acetate manufacturing from glucose and coupling to mitochondrial metabolism in mammals. Cell 175, 502–513 (2018).
Google Scholar
Röhrig, F. & Schulze, A. The multifaceted roles of fatty acid synthesis in most cancers. Nat. Rev. Most cancers 16, 732–749 (2016).
Google Scholar
Jones, M. E., Lipmann, F., Hilz, H. & Lynen, F. On the enzymatic mechanism of coenzyme A acetylation with adenosine triphosphate and acetate. J. Am. Chem. Soc. 75, 3285–3286 (1953).
Google Scholar
Kanehisa, M. & Goto, S. KEGG: Kyoto Encyclopedia of Genes and Genomes. Nucleic Acids Res. 28, 27–30 (2000).
Google Scholar
Mense, S. M. et al. Gene expression profiling reveals the profound upregulation of hypoxia-responsive genes in major human astrocytes. Physiol. Genomics 25, 435–449 (2006).
Google Scholar
Horton, J. D., Goldstein, J. L. & Brown, M. S. SREBPs: activators of the entire program of ldl cholesterol and fatty acid synthesis within the liver. J. Clin. Make investments. 109, 1125–1131 (2002).
Google Scholar
Davidson, S. M. et al. Atmosphere impacts the metabolic dependencies of Ras-driven non-small cell lung most cancers. Cell Metab. 23, 517–528 (2016).
Google Scholar
Davidson, S. M. et al. Direct proof for cancer-cell-autonomous extracellular protein catabolism in pancreatic tumors. Nat. Med. 23, 235–241 (2017).
Google Scholar
Sullivan, M. R. et al. Elevated serine synthesis gives a bonus for tumors arising in tissues the place serine ranges are limiting. Cell Metab. 29, 1410–1421 (2019).
Google Scholar
Savino, A. M. et al. Metabolic adaptation of acute lymphoblastic leukemia to the central nervous system microenvironment is dependent upon stearoyl-CoA desaturase. Nat. Most cancers 1, 998–1009 (2020).
Google Scholar
Jin, X. et al. A metastasis map of human most cancers cell traces. Nature 588, 331–336 (2020).
Google Scholar
Summons, R. E., Bradley, A. S., Jahnke, L. L. & Waldbauer, J. R. Steroids, triterpenoids and molecular oxygen. Philos. Trans. R. Soc. Lond. B Biol. Sci. 361, 951–968 (2006).
Google Scholar
Maddocks, O. D. Okay. et al. Modulating the therapeutic response of tumours to dietary serine and glycine hunger. Nature 544, 372–376 (2017).
Google Scholar
Li, L. et al. Identification of DHODH as a therapeutic goal in small-cell lung most cancers. Sci. Transl. Med. 11, eaaw7852 (2019).
Google Scholar
Sousa, C. M. et al. Pancreatic stellate cells assist tumour metabolism via autophagic alanine secretion. Nature 536, 479–483 (2016).
Google Scholar
Parker, S. J. et al. Selective alanine transporter utilization creates a targetable metabolic area of interest in pancreatic most cancers. Most cancers Discov. 10, 1018–1037 (2020).
Google Scholar
Hsueh, E. C. et al. Deprivation of arginine by recombinant human arginase in prostate most cancers cells. J. Hematol. Oncol. 5, 17 (2012).
Google Scholar
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