Prof Eyal Gottlieb
- Director of the Beatson Cancer Metabolism Research Unit (Beatson Institute for Cancer Research)
email: Eyal.Gottlieb@glasgow.ac.uk
Energy metabolism is defined as the reactions from which cells obtain and expend ATP. Our lab investigates the role of altered energy metabolism in supporting cancer development and in regulating cell death. The major routes of ATP generation in cells are glycolysis in the cytosol and oxidative phosphorylation in mitochondria. Although tightly-controlled energy metabolism is fundamental to survival, many types of cancer paradoxically exhibit abnormal glycolysis or mitochondrial activity in the face of high growth and proliferation rates. In fact, in cancer cells ATP can be predominantly derived from glycolysis, a significantly less efficient route of ATP production compared to oxidative phosphorylation.
Link to Apoptosis and Tumour Metabolism website
Article
Gonzalvez, F. et al. (2013) Barth syndrome: cellular compensation of mitochondrial dysfunction and apoptosis inhibition due to changes in cardiolipin remodeling linked to tafazzin (TAZ) gene mutation. Biochimica et Biophysica Acta: Molecular Basis of Disease, 1832 (8). pp. 1194-1206. ISSN 0925-4439 (doi:10.1016/j.bbadis.2013.03.005)
Gonzalvez, F. et al. (2013) Barth syndrome: cellular compensation of mitochondrial dysfunction and apoptosis inhibition due to changes in cardiolipin remodeling linked to tafazzin gene mutation. Biochimica et Biophysica Acta: Molecular Basis of Disease, 1832 (8). pp. 1194-1206. ISSN 0925-4439 (doi:10.1016/j.bbadis.2013.03.005)
Kaplon, J. et al. (2013) A key role for mitochondrial gatekeeper pyruvate dehydrogenase in oncogene-induced senescence. Nature, 498 (7452). pp. 109-112. ISSN 0028-0836 (doi:10.1038/nature12154)
Long, J.S., Crighton, D., O’Prey, J., MacKay, G., Zheng, L., Palmer, T.M., Gottlieb, E., and Ryan, K.M. (2013) Extracellular adenosine sensing—a metabolic cell death priming mechanism downstream of p53. Molecular Cell, 50 (3). pp. 394-406. ISSN 1097-2765 (doi:10.1016/j.molcel.2013.03.016)
Tannahill, G.M. et al. (2013) Succinate is an inflammatory signal that induces IL-1β through HIF-1α. Nature, 496 (7444). pp. 238-242. ISSN 0028-0836 (doi:10.1038/nature11986)
Maddocks, O.D.K., Berkers, C.R., Mason, S.M., Zheng, L., Blyth, K., Gottlieb, E., and Vousden, K.H. (2013) Serine starvation induces stress and p53-dependent metabolic remodelling in cancer cells. Nature, 493 (7433). pp. 542-546. ISSN 0028-0836 (doi:10.1038/nature11743)
Duran, R.V., MacKenzie, E.D., Boulahbel, H., Frezza, C., Heiserich, L., Tardito, S., Rocha, S., Hall, M.N., and Gottlieb, E. (2013) HIF-independent role of Prolyl Hydroxylases in the cellular response to amino acids. Oncogene . ISSN 0950-9232 (In Press)
Jalmar, O. et al. (2013) Caspase-8 binding to cardiolipin in giant unilamellar vesicles provides a functional docking platform for bid. PLoS ONE, 8 (2). e55250. ISSN 1932-6203 (doi:10.1371/journal.pone.0055250)
Chaneton, B., and Gottlieb, E. (2012) PGAMgnam style: a glycolytic switch controls biosynthesis. Cancer Cell, 22 (5). pp. 565-566. ISSN 1535-6108 (doi:10.1016/j.ccr.2012.10.014)
Chaneton, B. et al. (2012) Serine is a natural ligand and allosteric activator of pyruvate kinase M2. Nature, 491 (7424). pp. 458-462. ISSN 0028-0836 (doi:10.1038/nature11540)
Chaneton, B., and Gottlieb, E. (2012) Rocking cell metabolism: revised functions of the key glycolytic regulator PKM2 in cancer. Trends in Biochemical Sciences, 37 (8). pp. 309-316. ISSN 0968-0004 (doi:10.1016/j.tibs.2012.04.003)
Duran, R.V., Oppliger, W., Robitaille, A.M., Heiserich, L., Skendaj, R., Gottlieb, E., and Hall, M.N. (2012) Glutaminolysis activates Rag-mTORC1 signaling. Molecular Cell, 47 (3). pp. 349-358. ISSN 1097-2765 (doi:10.1016/j.molcel.2012.05.043)
Galluzzi, L. et al. (2012) Molecular definitions of cell death subroutines: recommendations of the Nomenclature Committee on Cell Death 2012. Cell Death and Differentiation, 19 (1). pp. 107-120. ISSN 1350-9047 (doi:10.1038/cdd.2011.96)
Schug, Z.T., Frezza, C., Galbraith, L.C.A., and Gottlieb, E. (2012) The music of lipids: how lipid composition orchestrates cellular behaviour. Acta Oncologica, 51 (3). pp. 301-310. ISSN 0284-186X (doi:10.3109/0284186X.2011.643823)
Frezza, C. et al. (2011) Haem oxygenase is synthetically lethal with the tumour suppressor fumarate hydratase. Nature, 477 (7363). pp. 225-228. ISSN 0028-0836 (doi:10.1038/nature10363)
Folger, O., Jerby, L., Frezza, C., Gottlieb, E., Ruppin, E., and Shlomi, T. (2011) Predicting selective drug targets in cancer through metabolic networks. Molecular Systems Biology, 7 . p. 517. ISSN 1744-4292 (doi:10.1038/msb.2011.51)
Frezza, C., Pollard, P.J., and Gottlieb, E. (2011) Inborn and acquired metabolic defects in cancer. Journal of Molecular Medicine, 89 (3). pp. 213-220. ISSN 0946-2716 (doi:10.1007/s00109-011-0728-4)
Folger, O., Jerby, L., Frezza, C., Gottlieb, E., Ruppin, E., and Shlomi, T. (2011) Predicting selective drug targets in cancer through metabolic networks. Molecular Systems Biology, 7 . p. 501. ISSN 1744-4292 (doi:10.1038/msb.2011.35)
Frezza, C., Zheng, L., Tennant, D.A., Papkovsky, D.B., Hedley, B., Kalna, G., Watson, D.G., and Gottlieb, E. (2011) Metabolic profiling of hypoxic cells revealed a catabolic signature required for cell survival. PLoS ONE, 6 (9). e24411. ISSN 1932-6203 (doi:10.1371/journal.pone.0024411)
Gottlieb, E. (2011) p53 guards the metabolic pathway less travelled. Nature Cell Biology, 13 (3). pp. 195-197. ISSN 1465-7392 (doi:10.1038/ncb2177)
Schug, Z.T., Gonzalvez, F., Houtkooper, R.H., Vaz, F.M., and Gottlieb, E. (2011) BID is cleaved by caspase-8 within a native complex on the mitochondrial membrane. Cell Death and Differentiation, 18 (3). pp. 538-548. ISSN 1350-9047 (doi:10.1038/cdd.2010.135)
Shlomi, T., Benyamini, T., Gottlieb, E., Sharan, R., and Ruppin, E. (2011) Genome-scale metabolic modeling elucidates the role of proliferative adaptation in causing the Warburg effect. PLoS Computational Biology, 7 (3). e1002018. ISSN 1553-734X (doi:10.1371/journal.pcbi.1002018)
Frezza, C., Tennant, D.A., and Gottlieb, E. (2010) IDH1 Mutations in Gliomas: When an Enzyme Loses Its Grip. Cancer Cell, 17 (1). pp. 7-9. ISSN 15356108 (doi:10.1016/j.ccr.2009.12.031)
Gottlieb, E, and Vousden, K. H. (2010) p53 Regulation of Metabolic Pathways. Cold Spring Harbor Perspectives in Biology, 2 (4). a001040. ISSN 1943-0264 (doi:10.1101/cshperspect.a001040)
Tennant, D.A., Duran, R.V., and Gottlieb, E. (2010) Targeting metabolic transformation for cancer therapy. Nature Reviews Cancer, 10 (4). pp. 267-277. ISSN 1474-175X (doi:10.1038/nrc2817)
Tennant, D.A., and Gottlieb, E. (2010) HIF prolyl hydroxylase-3 mediates alpha-ketoglutarate-induced apoptosis and tumor suppression. Journal of Molecular Medicine, 88 (8). pp. 839-849. ISSN 0946-2716 (doi:10.1007/s00109-010-0627-0)
Boulahbel, H., Duran, R.V., and Gottlieb, E. (2009) Prolyl hydroxylases as regulators of cell metabolism. Biochemical Society Transactions, 37 (1). pp. 291-294. ISSN 0300-5127 (doi:10.1042/BST0370291)
Frezza, C., and Gottlieb, E. (2009) Mitochondria in cancer: Not just innocent bystanders. Seminars in Cancer Biology, 19 (1). pp. 4-11. ISSN 1044579X (doi:10.1016/j.semcancer.2008.11.008)
Gottlieb, E. (2009) Cancer: The fat and the furious. Nature, 461 (7260). pp. 44-45. ISSN 0028-0836 (doi:10.1038/461044a)
King, A., and Gottlieb, E. (2009) Glucose metabolism and programmed cell death: an evolutionary and mechanistic perspective. Current Opinion in Cell Biology, 21 (6). pp. 885-893. ISSN 09550674 (doi:10.1016/j.ceb.2009.09.009)
Schug, Z.T., and Gottlieb, E. (2009) Cardiolipin acts as a mitochondrial signalling platform to launch apoptosis. Biochimica et Biophysica Acta (BBA): Biomembranes, 1788 (10). pp. 2022-2031. ISSN 00052736 (doi:10.1016/j.bbamem.2009.05.004)
Tennant, D. A., Duran, R. V., Boulahbel, H., and Gottlieb, E. (2009) Metabolic transformation in cancer. Carcinogenesis, 30 (8). pp. 1269-1280. ISSN 0143-3334 (doi:10.1093/carcin/bgp070)
Tennant, D.A. et al. (2009) Reactivating HIF prolyl hydroxylases under hypoxia results in metabolic catastrophe and cell death. Oncogene, 28 (45). pp. 4009-4021. ISSN 0950-9232 (doi:10.1038/onc.2009.250)
Gonzalvez, F., Schug, Z.T., Houtkooper, R. H., MacKenzie, E. D., Brooks, D. G., Wanders, R. J.A., Petit, P. X., Vaz, F. M., and Gottlieb, E. (2008) Cardiolipin provides an essential activating platform for caspase-8 on mitochondria. Journal of Cell Biology, 183 (4). pp. 681-696. ISSN 0021-9525 (doi:10.1083/jcb.200803129)
Gottlieb, E, and Gonzalvez, F (2007) Cardiolipin: Setting the beat of apoptosis. Apoptosis, 12 (5). pp. 877-885. ISSN 1360-8185 (doi:10.1007/s10495-007-0718-8)
MacKenzie, ED, Selak, MA, Tennant, DA, Payne, LJ, Crosby, S, Frederiksen, CM, Watson, DG, and Gottlieb, E (2007) Cell-permeating alpha-ketoglutarate derivatives alleviate pseudohypoxia in succinate dehydrogenase-deficient cells. Molecular and Cellular Biology, 27 (9). pp. 3282-3289. ISSN 0270-7306 (doi:10.1128/MCB.01927-06 )
Bensaad, K, Tsuruta, A, Selak, MA, Vidal, MNC, Nakano, K, Bartrons, R, Gottlieb, E, and Vousden, KH (2006) TIGAR, a p53-inducible regulator of glycolysis and apoptosis. Cell, 126 (1). pp. 107-120. ISSN 0092-8674 (doi:10.1016/j.cell.2006.05.036 )
Gottlieb, E (2006) OPA1 and PARL keep a lid on apoptosis. Cell, 126 (1). pp. 27-29. ISSN 0092-8674 (doi:10.1016/j.cell.2006.06.030)
King, A, Selak, MA, and Gottlieb, E (2006) Succinate dehydrogenase and fumarate hydratase: linking mitochondrial dysfunction and cancer. Oncogene, 25 (34). pp. 4675-4682. ISSN 0950-9232 (doi:10.1038/sj.onc.1209594 )
Selak, M.A., Duran, R.V., and Gottlieb, E. (2006) Redox stress is not essential for the pseudo-hypoxic phenotype of succinate dehydrogenase deficient cells. Biochimica et Biophysica Acta: Bioenergetics, 1757 (5-6). pp. 567-572. ISSN 0005-2728 (doi:10.1016/j.bbabio.2006.05.015 )
Gottlieb, E, and Tomlinson, IPM (2005) Mitochondrial tumour suppressors: A genetic and biochemical update. Nature Reviews Cancer, 5 (11). pp. 857-866. ISSN 1474-175X (doi:10.1038/nrc1737 )
Selak, MA, Armour, SM, MacKenzie, ED, Boulahbel, H, Watson, DG, Mansfield, KD, Pan, Y, Simon, MC, Thompson, CB, and Gottlieb, E (2005) Succinate links TCA cycle dysfunction to oncogenesis by inhibiting HIF-α prolyl hydroxylase. Cancer Cell, 7 (1). pp. 77-85. ISSN 1535-6108 (doi:10.1016/j.ccr.2004.11.022)
Grants and Awards listed are those received whilst working with the University of Glasgow.
- Metabolic vulnerabilities induced by Myc
Cancer Research UK
2012 - 2013