The Emerging Facets of Non-Cancerous Warburg Effect

Lunt, 2011, Aerobic glycolysis: meeting the metabolic requirements of cell proliferation, Annu Rev Cell Dev Biol, 27, 441, 10.1146/annurev-cellbio-092910-154237

O’Neill, 2013, Metabolism of inflammation limited by AMPK and pseudo-starvation, Nature, 493, 346, 10.1038/nature11862

Warburg, 1956, On the origin of cancer cells, Science, 123, 309, 10.1126/science.123.3191.309

Vander Heiden, 2009, Understanding the Warburg effect: the metabolic requirements of cell proliferation, Science, 324, 1029, 10.1126/science.1160809

Takubo, 2013, Regulation of glycolysis by Pdk functions as a metabolic checkpoint for cell cycle quiescence in hematopoietic stem cells, Cell Stem Cell, 12, 49, 10.1016/j.stem.2012.10.011

Varum, 2011, Energy metabolism in human pluripotent stem cells and their differentiated counterparts, PLoS One, 6, e20914, 10.1371/journal.pone.0020914

Zielinski, 2017, Systems biology analysis of drivers underlying hallmarks of cancer cell metabolism, Sci Rep, 7, 41241, 10.1038/srep41241

Hanahan, 2011, Hallmarks of cancer: the next generation, Cell, 144, 646, 10.1016/j.cell.2011.02.013

McKee, 2010, Immune mechanisms of protection: can adjuvants rise to the challenge?, BMC Biol, 8, 37, 10.1186/1741-7007-8-37

BMC2014

Human Tissue2017

Macintyre, 2014, The glucose transporter Glut1 is selectively essential for CD4 T cell activation and effector function, Cell Metab, 20, 61, 10.1016/j.cmet.2014.05.004

Mahata, 2014, Single-cell RNA sequencing reveals T helper cells synthesizing steroids de novo to contribute to immune homeostasis, Cell Rep, 7, 1130, 10.1016/j.celrep.2014.04.011

van der Windt, 2012, Metabolic switching and fuel choice during T-cell differentiation and memory development, Immunol Rev, 249, 27, 10.1111/j.1600-065X.2012.01150.x

Palmer, 2015, Glucose metabolism regulates T cell activation, differentiation, and functions, Front Immunol, 6, 1, 10.3389/fimmu.2015.00001

Wang, 2012, Metabolic checkpoints in activated T cells, Nat Immunol, 13, 907, 10.1038/ni.2386

Jacobs, 2008, Glucose uptake is limiting in T cell activation and requires CD28-mediated Akt-dependent and independent pathways, J Immunol, 180, 4476, 10.4049/jimmunol.180.7.4476

Michalek, 2011, Cutting edge: distinct glycolytic and lipid oxidative metabolic programs are essential for effector and regulatory CD4+ T cell subsets, J Immunol, 186, 3299, 10.4049/jimmunol.1003613

Ostroukhova, 2012, The role of low-level lactate production in airway inflammation in asthma, Am J Physiol Lung Cell Mol Physiol, 302, L300, 10.1152/ajplung.00221.2011

Gerriets, 2012, Metabolic pathways in T cell fate and function, Trends Immunol, 33, 168, 10.1016/j.it.2012.01.010

Frezza, 2009, Mitochondria in cancer: not just innocent bystanders, Semin Cancer Biol, 19, 4, 10.1016/j.semcancer.2008.11.008

Sinclair, 2013, Control of amino-acid transport by antigen receptors coordinates the metabolic reprogramming essential for T cell differentiation, Nat Immunol, 14, 500, 10.1038/ni.2556

Zu, 2004, Cancer metabolism: facts, fantasy, and fiction, Biochem Biophys Res Commun, 313, 459, 10.1016/j.bbrc.2003.11.136

Herbel, 2016, Clinical significance of T cell metabolic reprogramming in cancer, Clin Transl Med, 5, 29, 10.1186/s40169-016-0110-9

Sakaguchi, 2012, Re-establishing immunological self-tolerance in autoimmune disease, Nat Med, 18, 54, 10.1038/nm.2622

Cho, 2015, Heterogeneity of autoimmune diseases: pathophysiologic insights from genetics and implications for new therapies, Nat Med, 21, 730, 10.1038/nm.3897

De Bock, 2013, Role of PFKFB3-driven glycolysis in vessel sprouting, Cell, 154, 651, 10.1016/j.cell.2013.06.037

Almeida, 2010, E3 ubiquitin ligase APC/C-Cdh1 accounts for the Warburg effect by linking glycolysis to cell proliferation, Proc Natl Acad Sci U S A, 107, 738, 10.1073/pnas.0913668107

Newsholme, 1986, Metabolism of glucose, glutamine, long-chain fatty acids and ketone bodies by murine macrophages, Biochem J, 239, 121, 10.1042/bj2390121

Luo, 2010, AMPK as a metabolic tumor suppressor: control of metabolism and cell growth, Future Oncol, 6, 457, 10.2217/fon.09.174

Li, 2015, Targeting AMPK for cancer prevention and treatment, Oncotarget, 6, 7365, 10.18632/oncotarget.3629

Ito, 2014, Metabolic requirements for the maintenance of self-renewing stem cells, Nat Rev Mol Cell Biol, 15, 243, 10.1038/nrm3772

Voisinne, 2015, T cells integrate local and global cues to discriminate between structurally similar antigens, Cell Rep, 11, 1208, 10.1016/j.celrep.2015.04.051

Patsch, 2015, Generation of vascular endothelial and smooth muscle cells from human pluripotent stem cells, Nat Cell Biol, 17, 994, 10.1038/ncb3205

Schoors, 2015, Fatty acid carbon is essential for dNTP synthesis in endothelial cells, Nature, 520, 192, 10.1038/nature14362

Clem, 2013, Targeting 6-phosphofructo-2-kinase (PFKFB3) as a therapeutic strategy against cancer, Mol Cancer Ther, 12, 1461, 10.1158/1535-7163.MCT-13-0097

Klarer, 2014, Inhibition of 6-phosphofructo-2-kinase (PFKFB3) induces autophagy as a survival mechanism, Cancer Metab, 2, 2, 10.1186/2049-3002-2-2

Folmes, 2011, Somatic oxidative bioenergetics transitions into pluripotency-dependent glycolysis to facilitate nuclear reprogramming, Cell Metab, 14, 264, 10.1016/j.cmet.2011.06.011

Kondoh, 2007, A high glycolytic flux supports the proliferative potential of murine embryonic stem cells, Antioxid Redox Signal, 9, 293, 10.1089/ars.2006.1467

Chung, 2007, Mitochondrial oxidative metabolism is required for the cardiac differentiation of stem cells, Nat Clin Pract Cardiovasc Med, 4, S60, 10.1038/ncpcardio0766

Chen, 2008, TSC-mTOR maintains quiescence and function of hematopoietic stem cells by repressing mitochondrial biogenesis and reactive oxygen species, J Exp Med, 205, 2397, 10.1084/jem.20081297

Cho, 2006, Dynamic changes in mitochondrial biogenesis and antioxidant enzymes during the spontaneous differentiation of human embryonic stem cells, Biochem Biophys Res Commun, 348, 1472, 10.1016/j.bbrc.2006.08.020

St John, 2005, The expression of mitochondrial DNA transcription factors during early cardiomyocyte in vitro differentiation from human embryonic stem cells, Cloning Stem Cells, 7, 141, 10.1089/clo.2005.7.141

Shyh-Chang, 2013, Stem cell metabolism in tissue development and aging, Development, 140, 2535, 10.1242/dev.091777

Pantaleon, 1998, Glucose transporters in preimplantation development, Rev Reprod, 3, 77, 10.1530/ror.0.0030077

Pedersen, 2007, Warburg, me and hexokinase 2: multiple discoveries of key molecular events underlying one of cancers’ most common phenotypes, the “Warburg Effect”, i.e., elevated glycolysis in the presence of oxygen, J Bioenerg Biomembr, 39, 211, 10.1007/s10863-007-9094-x

Leese, 1984, Pyruvate and glucose uptake by mouse ova and preimplantation embryos, J Reprod Fertil, 72, 9, 10.1530/jrf.0.0720009

Hansson, 2012, Highly coordinated proteome dynamics during reprogramming of somatic cells to pluripotency, Cell Rep, 2, 1579, 10.1016/j.celrep.2012.10.014

Shyh-Chang, 2013, Influence of threonine metabolism on S-adenosylmethionine and histone methylation, Science, 339, 222, 10.1126/science.1226603

Yalcin, 2014, 6-Phosphofructo-2-kinase (PFKFB3) promotes cell cycle progression and suppresses apoptosis via Cdk1-mediated phosphorylation of p27, Cell Death Dis, 5, e1337, 10.1038/cddis.2014.292

Srivastava, 2016, Stage-specific changes in Plasmodium metabolism required for differentiation and adaptation to different host and vector environments, PLoS Pathog, 12, e1006094, 10.1371/journal.ppat.1006094

Josling, 2015, Sexual development in Plasmodium parasites: knowing when it’s time to commit, Nat Rev Microbiol, 13, 573, 10.1038/nrmicro3519

MacRae, 2013, Mitochondrial metabolism of sexual and asexual blood stages of the malaria parasite Plasmodium falciparum, BMC Biol, 11, 67, 10.1186/1741-7007-11-67

Sturm, 2015, Mitochondrial ATP synthase is dispensable in blood-stage Plasmodium berghei rodent malaria but essential in the mosquito phase, Proc Natl Acad Sci U S A, 112, 10216, 10.1073/pnas.1423959112

Ke, 2015, Genetic investigation of tricarboxylic acid metabolism during the Plasmodium falciparum life cycle, Cell Rep, 11, 164, 10.1016/j.celrep.2015.03.011

Gardner, 2002, Genome sequence of the human malaria parasite Plasmodium falciparum, Nature, 419, 498, 10.1038/nature01097

Schellenberger, 2011, Quantitative prediction of cellular metabolism with constraint-based models: the COBRA Toolbox v2.0, Nat Protoc, 6, 1290, 10.1038/nprot.2011.308

Lewis, 2012, Constraining the metabolic genotype-phenotype relationship using a phylogeny of in silico methods, Nat Rev Microbiol, 10, 291, 10.1038/nrmicro2737

Oberhardt, 2013, Metabolically re-modeling the drug pipeline, Curr Opin Pharmacol, 13, 778, 10.1016/j.coph.2013.05.006

Lewis, 2013, The evolution of genome-scale models of cancer metabolism, Front Physiol, 4, 237, 10.3389/fphys.2013.00237

Shlomi, 2011, Genome-scale metabolic modeling elucidates the role of proliferative adaptation in causing the Warburg effect, PLoS Comput Biol, 7, e1002018, 10.1371/journal.pcbi.1002018

Dai, 2016, A flux balance of glucose metabolism clarifies the requirements of the Warburg effect, Biophys J, 111, 1088, 10.1016/j.bpj.2016.07.028

Bordbar, 2014, Constraint-based models predict metabolic and associated cellular functions, Nat Rev Genet, 15, 107, 10.1038/nrg3643

Opdam, 2017, A systematic evaluation of methods for tailoring genome-scale metabolic models, Cell Syst, 4, 318, 10.1016/j.cels.2017.01.010

Machado, 2014, Systematic evaluation of methods for integration of transcriptomic data into constraint-based models of metabolism, PLoS Comput Biol, 10, e1003580, 10.1371/journal.pcbi.1003580

Folger, 2011, Predicting selective drug targets in cancer through metabolic networks, Mol Syst Biol, 7, 501, 10.1038/msb.2011.35

Frezza, 2011, Haem oxygenase is synthetically lethal with the tumour suppressor fumarate hydratase, Nature, 477, 225, 10.1038/nature10363

Yizhak, 2014, A computational study of the Warburg effect identifies metabolic targets inhibiting cancer migration, Mol Syst Biol, 10, 744, 10.15252/msb.20134993

Kim, 2011, Integrative genome-scale metabolic analysis of Vibrio vulnificus for drug targeting and discovery, Mol Syst Biol, 7, 460, 10.1038/msb.2010.115

Lewis, 2010, Large-scale in silico modeling of metabolic interactions between cell types in the human brain, Nat Biotechnol, 28, 1279, 10.1038/nbt.1711

Galluzzi, 2013, Metabolic targets for cancer therapy, Nat Rev Drug Discov, 12, 829, 10.1038/nrd4145

Vander Heiden, 2013, Exploiting tumor metabolism: challenges for clinical translation, J Clin Invest, 123, 3648, 10.1172/JCI72391

Shestov, 2014, Quantitative determinants of aerobic glycolysis identify flux through the enzyme GAPDH as a limiting step, Elife, 3, 10.7554/eLife.03342

Hartwell, 2013, Niche-based screening identifies small-molecule inhibitors of leukemia stem cells, Nat Chem Biol, 9, 840, 10.1038/nchembio.1367

Gazzerro, 2012, Pharmacological actions of statins: a critical appraisal in the management of cancer, Pharmacol Rev, 64, 102, 10.1124/pr.111.004994