Acidosis Drives the Reprogramming of Fatty Acid Metabolism in Cancer Cells through Changes in Mitochondrial and Histone Acetylation

Abu-Elheiga, 2000, The subcellular localization of acetyl-CoA carboxylase 2, Proc. Natl. Acad. Sci. USA, 97, 1444, 10.1073/pnas.97.4.1444 Ahn, 2008, A role for the mitochondrial deacetylase Sirt3 in regulating energy homeostasis, Proc. Natl. Acad. Sci. USA, 105, 14447, 10.1073/pnas.0803790105 Boidot, 2014, A generic cycling hypoxia-derived prognostic gene signature: application to breast cancer profiling, Oncotarget, 5, 6947, 10.18632/oncotarget.2285 Brahimi-Horn, 2011, Hypoxia and energetic tumour metabolism, Curr. Opin. Genet. Dev., 21, 67, 10.1016/j.gde.2010.10.006 Chen, 2008, The genomic analysis of lactic acidosis and acidosis response in human cancers, PLoS Genet., 4, e1000293, 10.1371/journal.pgen.1000293 Choudhary, 2014, The growing landscape of lysine acetylation links metabolism and cell signalling, Nat. Rev. Mol. Cell Biol., 15, 536, 10.1038/nrm3841 Corbet, 2015, Metabolic and mind shifts: from glucose to glutamine and acetate addictions in cancer, Curr. Opin. Clin. Nutr. Metab. Care, 18, 346, 10.1097/MCO.0000000000000178 Corbet, 2014, The SIRT1/HIF2α axis drives reductive glutamine metabolism under chronic acidosis and alters tumor response to therapy, Cancer Res., 74, 5507, 10.1158/0008-5472.CAN-14-0705 Currie, 2013, Cellular fatty acid metabolism and cancer, Cell Metab., 18, 153, 10.1016/j.cmet.2013.05.017 Fendt, 2013, Reductive glutamine metabolism is a function of the α-ketoglutarate to citrate ratio in cells, Nat. Commun., 4, 2236, 10.1038/ncomms3236 Foster, 2012, Malonyl-CoA: the regulator of fatty acid synthesis and oxidation, J. Clin. Invest., 122, 1958, 10.1172/JCI63967 Gatenby, 2008, A microenvironmental model of carcinogenesis, Nat. Rev. Cancer, 8, 56, 10.1038/nrc2255 Gertz, 2013, Ex-527 inhibits Sirtuins by exploiting their unique NAD+-dependent deacetylation mechanism, Proc. Natl. Acad. Sci. USA, 110, E2772, 10.1073/pnas.1303628110 Harjes, 2016, Targeting fatty acid metabolism in cancer and endothelial cells, Crit. Rev. Oncol. Hematol., 97, 15, 10.1016/j.critrevonc.2015.10.011 Hashim, 2011, Imaging pH and metastasis, NMR Biomed., 24, 582, 10.1002/nbm.1644 Hebert, 2013, Calorie restriction and SIRT3 trigger global reprogramming of the mitochondrial protein acetylome, Mol. Cell, 49, 186, 10.1016/j.molcel.2012.10.024 Hirschey, 2010, SIRT3 regulates mitochondrial fatty-acid oxidation by reversible enzyme deacetylation, Nature, 464, 121, 10.1038/nature08778 Hue, 2009, The Randle cycle revisited: a new head for an old hat, Am. J. Physiol. Endocrinol. Metab., 297, E578, 10.1152/ajpendo.00093.2009 Kamphorst, 2014, Quantitative analysis of acetyl-CoA production in hypoxic cancer cells reveals substantial contribution from acetate, Cancer Metab., 2, 23, 10.1186/2049-3002-2-23 Kokkonen, 2014, Studying SIRT6 regulation using H3K56 based substrate and small molecules, Eur. J. Pharm. Sci., 63, 71, 10.1016/j.ejps.2014.06.015 Lamonte, 2013, Acidosis induces reprogramming of cellular metabolism to mitigate oxidative stress, Cancer Metab., 1, 23, 10.1186/2049-3002-1-23 Mashimo, 2014, Acetate is a bioenergetic substrate for human glioblastoma and brain metastases, Cell, 159, 1603, 10.1016/j.cell.2014.11.025 McBrian, 2013, Histone acetylation regulates intracellular pH, Mol. Cell, 49, 310, 10.1016/j.molcel.2012.10.025 Metallo, 2012, Reductive glutamine metabolism by IDH1 mediates lipogenesis under hypoxia, Nature, 481, 380, 10.1038/nature10602 Morita, 1992, Clastogenicity of low pH to various cultured mammalian cells, Mutat. Res., 268, 297, 10.1016/0027-5107(92)90235-T Mullen, 2012, Reductive carboxylation supports growth in tumour cells with defective mitochondria, Nature, 481, 385, 10.1038/nature10642 Palmieri, 2015, Acetylation of human mitochondrial citrate carrier modulates mitochondrial citrate/malate exchange activity to sustain NADPH production during macrophage activation, Biochim. Biophys. Acta, 1847, 729, 10.1016/j.bbabio.2015.04.009 Pietrocola, 2015, Acetyl coenzyme A: a central metabolite and second messenger, Cell Metab., 21, 805, 10.1016/j.cmet.2015.05.014 Polet, 2013, Endothelial cell metabolism and tumour angiogenesis: glucose and glutamine as essential fuels and lactate as the driving force, J. Intern. Med., 273, 156, 10.1111/joim.12016 Schug, 2015, Acetyl-CoA synthetase 2 promotes acetate utilization and maintains cancer cell growth under metabolic stress, Cancer Cell, 27, 57, 10.1016/j.ccell.2014.12.002 Scott, 2012, Identification of a molecular component of the mitochondrial acetyltransferase programme: a novel role for GCN5L1, Biochem. J., 443, 655, 10.1042/BJ20120118 Someya, 2010, Sirt3 mediates reduction of oxidative damage and prevention of age-related hearing loss under caloric restriction, Cell, 143, 802, 10.1016/j.cell.2010.10.002 Su, 2009, Cellular fatty acid uptake: a pathway under construction, Trends Endocrinol. Metab., 20, 72, 10.1016/j.tem.2008.11.001 Sullivan, 2014, Mitochondrial reactive oxygen species and cancer, Cancer Metab., 2, 17, 10.1186/2049-3002-2-17 Vander Heiden, 2009, Understanding the Warburg effect: the metabolic requirements of cell proliferation, Science, 324, 1029, 10.1126/science.1160809 Wise, 2011, Hypoxia promotes isocitrate dehydrogenase-dependent carboxylation of α-ketoglutarate to citrate to support cell growth and viability, Proc. Natl. Acad. Sci. USA, 108, 19611, 10.1073/pnas.1117773108 Yang, 2014, Glutamine oxidation maintains the TCA cycle and cell survival during impaired mitochondrial pyruvate transport, Mol. Cell, 56, 414, 10.1016/j.molcel.2014.09.025