Acuna-Hidalgo R, Schanze D, Kariminejad A, Nordgren A, Kariminejad MH, Conner P, Grigelioniene G, Nilsson D, Nordenskjold M, Wedell A, et al. Neu-Laxova syndrome is a heterogeneous metabolic disorder caused by defects in enzymes of the L-serine biosynthesis pathway. Am J Hum Genet. 2014;95:285–93.
Article
CAS
PubMed
PubMed Central
Google Scholar
Ahler E, Sullivan WJ, Cass A, Braas D, York AG, Bensinger SJ, Graeber TG, Christofk HR. Doxycycline alters metabolism and proliferation of human cell lines. PLoS One. 2013;8:e64561.
Article
CAS
PubMed
PubMed Central
Google Scholar
Beard C, Hochedlinger K, Plath K, Wutz A, Jaenisch R. Efficient method to generate single-copy transgenic mice by site-specific integration in embryonic stem cells. Genesis. 2006;44:23–8.
Article
CAS
PubMed
Google Scholar
Bennett BD, Yuan J, Kimball EH, Rabinowitz JD. Absolute quantitation of intracellular metabolite concentrations by an isotope ratio-based approach. Nat Protoc. 2008;3:1299–311.
Article
CAS
PubMed
PubMed Central
Google Scholar
Brookheart RT, Michel CI, Schaffer JE. As a matter of fat. Cell Metab. 2009;10:9–12.
Article
CAS
PubMed
PubMed Central
Google Scholar
Carey BW, Finley LW, Cross JR, Allis CD, Thompson CB. Intracellular alpha-ketoglutarate maintains the pluripotency of embryonic stem cells. Nature. 2015;518:413–6.
Article
CAS
PubMed
Google Scholar
DeNicola GM, Chen PH, Mullarky E, Sudderth JA, Hu Z, Wu D, Tang H, Xie Y, Asara JM, Huffman KE, et al. NRF2 regulates serine biosynthesis in non-small cell lung cancer. Nat Genet. 2015;47:1475–81.
Article
CAS
PubMed
PubMed Central
Google Scholar
Diehl FF, Lewis CA, Fiske BP, Vander Heiden MG. Cellular redox state constrains serine synthesis and nucleotide production to impact cell proliferation. Nat Metab. 2019;1:861–7.
Article
CAS
PubMed
PubMed Central
Google Scholar
Ding J, Li T, Wang X, Zhao E, Choi JH, Yang L, Zha Y, Dong Z, Huang S, Asara JM, et al. The histone H3 methyltransferase G9A epigenetically activates the serine-glycine synthesis pathway to sustain cancer cell survival and proliferation. Cell Metab. 2013;18:896–907.
Article
CAS
PubMed
Google Scholar
Dow LE, Nasr Z, Saborowski M, Ebbesen SH, Manchado E, Tasdemir N, Lee T, Pelletier J, Lowe SW. Conditional reverse tet-transactivator mouse strains for the efficient induction of TRE-regulated transgenes in mice. PLoS One. 2014;9:e95236.
Article
PubMed
PubMed Central
CAS
Google Scholar
Esaki K, Sayano T, Sonoda C, Akagi T, Suzuki T, Ogawa T, Okamoto M, Yoshikawa T, Hirabayashi Y, Furuya S. L-serine deficiency elicits intracellular accumulation of cytotoxic deoxysphingolipids and lipid body formation. J Biol Chem. 2015;290:14595–609.
Article
CAS
PubMed
PubMed Central
Google Scholar
Fellmann C, Hoffmann T, Sridhar V, Hopfgartner B, Muhar M, Roth M, Lai DY, Barbosa IA, Kwon JS, Guan Y, et al. An optimized microRNA backbone for effective single-copy RNAi. Cell Rep. 2013;5:1704–13.
Article
CAS
PubMed
Google Scholar
Gantner ML, Eade K, Wallace M, Handzlik MK, Fallon R, Trombley J, Bonelli R, Giles S, Harkins-Perry S, Heeren TFC, et al. Serine and lipid metabolism in macular disease and peripheral neuropathy. N Engl J Med. 2019;381:1422–33.
Article
CAS
PubMed
PubMed Central
Google Scholar
Gao X, Lee K, Reid MA, Sanderson SM, Qiu C, Li S, Liu J, Locasale JW. Serine availability influences mitochondrial dynamics and function through lipid metabolism. Cell Rep. 2018;22:3507–20.
Article
CAS
PubMed
PubMed Central
Google Scholar
Hitosugi T, Zhou L, Elf S, Fan J, Kang HB, Seo JH, Shan C, Dai Q, Zhang L, Xie J, et al. Phosphoglycerate mutase 1 coordinates glycolysis and biosynthesis to promote tumor growth. Cancer Cell. 2012;22:585–600.
Article
CAS
PubMed
PubMed Central
Google Scholar
Kalhan SC, Hanson RW. Resurgence of serine: an often neglected but indispensable amino Acid. J Biol Chem. 2012;287:19786–91.
Article
CAS
PubMed
PubMed Central
Google Scholar
Kang YP, Lee WJ, Hong JY, Lee SB, Park JH, Kim D, Park S, Park CS, Park SW, Kwon SW. Novel approach for analysis of bronchoalveolar lavage fluid (BALF) using HPLC-QTOF-MS-based lipidomics: lipid levels in asthmatics and corticosteroid-treated asthmatic patients. J Proteome Res. 2014;13:3919–29.
Article
CAS
PubMed
Google Scholar
Kang YP, Torrente L, Falzone A, Elkins CM, Liu M, Asara JM, Dibble CC, DeNicola GM. Cysteine dioxygenase 1 is a metabolic liability for non-small cell lung cancer. Elife. 2019;8.
Kim W, Deik A, Gonzalez C, Gonzalez ME, Fu F, Ferrari M, Churchhouse CL, Florez JC, Jacobs SBR, Clish CB, et al. Polyunsaturated fatty acid desaturation is a mechanism for glycolytic NAD(+) recycling. Cell Metab. 2019;29(856-870):e857.
Google Scholar
Labuschagne CF, van den Broek NJ, Mackay GM, Vousden KH, Maddocks OD. Serine, but not glycine, supports one-carbon metabolism and proliferation of cancer cells. Cell Rep. 2014;7:1248–58.
Article
CAS
PubMed
Google Scholar
Listenberger LL, Han X, Lewis SE, Cases S, Farese RV Jr, Ory DS, Schaffer JE. Triglyceride accumulation protects against fatty acid-induced lipotoxicity. Proc Natl Acad Sci U S A. 2003;100:3077–82.
Article
CAS
PubMed
PubMed Central
Google Scholar
Locasale JW, Grassian AR, Melman T, Lyssiotis CA, Mattaini KR, Bass AJ, Heffron G, Metallo CM, Muranen T, Sharfi H, et al. Phosphoglycerate dehydrogenase diverts glycolytic flux and contributes to oncogenesis. Nat Genet. 2011;43:869–74.
Article
CAS
PubMed
PubMed Central
Google Scholar
Lucchetti J, Fracasso C, Balducci C, Passoni A, Forloni G, Salmona M, Gobbi M. Plasma and brain concentrations of doxycycline after single and repeated doses in wild-type and APP23 mice. J Pharmacol Exp Ther. 2019;368:32–40.
Article
CAS
PubMed
Google Scholar
Ma L, Tao Y, Duran A, Llado V, Galvez A, Barger JF, Castilla EA, Chen J, Yajima T, Porollo A, et al. Control of nutrient stress-induced metabolic reprogramming by PKCzeta in tumorigenesis. Cell. 2013;152:599–611.
Article
CAS
PubMed
PubMed Central
Google Scholar
Maddocks OD, Berkers CR, Mason SM, Zheng L, Blyth K, Gottlieb E, Vousden KH. Serine starvation induces stress and p53-dependent metabolic remodelling in cancer cells. Nature. 2013;493:542–6.
Article
CAS
PubMed
Google Scholar
Maddocks OD, Labuschagne CF, Adams PD, Vousden KH. Serine metabolism supports the methionine cycle and DNA/RNA methylation through de novo ATP synthesis in cancer cells. Mol Cell. 2016;61:210–21.
Article
CAS
PubMed
PubMed Central
Google Scholar
Maddocks ODK, Athineos D, Cheung EC, Lee P, Zhang T, van den Broek NJF, Mackay GM, Labuschagne CF, Gay D, Kruiswijk F, et al. Modulating the therapeutic response of tumours to dietary serine and glycine starvation. Nature. 2017;544:372–6.
Article
CAS
PubMed
Google Scholar
Millard P, Letisse F, Sokol S, Portais JC. IsoCor: correcting MS data in isotope labeling experiments. Bioinformatics. 2012;28:1294–6.
Article
CAS
PubMed
Google Scholar
Mullarky E, Lucki NC, Beheshti Zavareh R, Anglin JL, Gomes AP, Nicolay BN, Wong JC, Christen S, Takahashi H, Singh PK, et al. Identification of a small molecule inhibitor of 3-phosphoglycerate dehydrogenase to target serine biosynthesis in cancers. Proc Natl Acad Sci U S A. 2016;113:1778–83.
Article
CAS
PubMed
PubMed Central
Google Scholar
Mullarky E, Xu J, Robin AD, Huggins DJ, Jennings A, Noguchi N, Olland A, Lakshminarasimhan D, Miller M, Tomita D, et al. Inhibition of 3-phosphoglycerate dehydrogenase (PHGDH) by indole amides abrogates de novo serine synthesis in cancer cells. Bioorg Med Chem Lett. 2019;29:2503–10.
Article
CAS
PubMed
PubMed Central
Google Scholar
Okabe K, Usui I, Yaku K, Hirabayashi Y, Tobe K, Nakagawa T. Deletion of PHGDH in adipocytes improves glucose intolerance in diet-induced obese mice. Biochem Biophys Res Commun. 2018;504:309–14.
Article
CAS
PubMed
Google Scholar
Ou Y, Wang SJ, Jiang L, Zheng B, Gu W. p53 Protein-mediated regulation of phosphoglycerate dehydrogenase (PHGDH) is crucial for the apoptotic response upon serine starvation. J Biol Chem. 2015;290:457–66.
Article
CAS
PubMed
Google Scholar
Pacold ME, Brimacombe KR, Chan SH, Rohde JM, Lewis CA, Swier LJ, Possemato R, Chen WW, Sullivan LB, Fiske BP, et al. A PHGDH inhibitor reveals coordination of serine synthesis and one-carbon unit fate. Nat Chem Biol. 2016;12:452–8.
Article
CAS
PubMed
PubMed Central
Google Scholar
Possemato R, Marks KM, Shaul YD, Pacold ME, Kim D, Birsoy K, Sethumadhavan S, Woo HK, Jang HG, Jha AK, et al. Functional genomics reveal that the serine synthesis pathway is essential in breast cancer. Nature. 2011;476:346–50.
Article
CAS
PubMed
PubMed Central
Google Scholar
Premsrirut PK, Dow LE, Kim SY, Camiolo M, Malone CD, Miething C, Scuoppo C, Zuber J, Dickins RA, Kogan SC, et al. A rapid and scalable system for studying gene function in mice using conditional RNA interference. Cell. 2011;145:145–58.
Article
CAS
PubMed
PubMed Central
Google Scholar
Schutzhold V, Hahn J, Tummler K, Klipp E. Computational modeling of lipid metabolism in yeast. Front Mol Biosci. 2016;3:57.
Article
PubMed
PubMed Central
CAS
Google Scholar
Shaheen R, Rahbeeni Z, Alhashem A, Faqeih E, Zhao Q, Xiong Y, Almoisheer A, Al-Qattan SM, Almadani HA, Al-Onazi N, et al. Neu-Laxova syndrome, an inborn error of serine metabolism, is caused by mutations in PHGDH. Am J Hum Genet. 2014;94:898–904.
Article
CAS
PubMed
PubMed Central
Google Scholar
Sim WC, Lee W, Sim H, Lee KY, Jung SH, Choi YJ, Kim HY, Kang KW, Lee JY, Choi YJ, et al. Downregulation of PHGDH expression and hepatic serine level contribute to the development of fatty liver disease. Metabolism. 2020;102:154000.
Article
PubMed
CAS
Google Scholar
Sullivan MR, Mattaini KR, Dennstedt EA, Nguyen AA, Sivanand S, Reilly MF, Meeth K, Muir A, Darnell AM, Bosenberg MW, et al. Increased serine synthesis provides an advantage for tumors arising in tissues where serine levels are limiting. Cell Metab. 2019;29(1410-1421):e1414.
Google Scholar
Tameire F, Verginadis II, Leli NM, Polte C, Conn CS, Ojha R, Salas Salinas C, Chinga F, Monroy AM, Fu W, et al. ATF4 couples MYC-dependent translational activity to bioenergetic demands during tumour progression. Nat Cell Biol. 2019;21:889–99.
Article
CAS
PubMed
PubMed Central
Google Scholar
Tsugawa H, Cajka T, Kind T, Ma Y, Higgins B, Ikeda K, Kanazawa M, VanderGheynst J, Fiehn O, Arita M. MS-DIAL: data-independent MS/MS deconvolution for comprehensive metabolome analysis. Nat Methods. 2015;12:523–6.
Article
CAS
PubMed
PubMed Central
Google Scholar
Vandekeere S, Dubois C, Kalucka J, Sullivan MR, Garcia-Caballero M, Goveia J, Chen R, Diehl FF, Bar-Lev L, Souffreau J, et al. Serine synthesis via PHGDH is essential for heme production in endothelial cells. Cell Metab. 2018;28(573-587):e513.
Google Scholar
Wang Q, Liberti MV, Liu P, Deng X, Liu Y, Locasale JW, Lai L. Rational design of selective allosteric inhibitors of PHGDH and serine synthesis with anti-tumor activity. Cell Chem Biol. 2017;24:55–65.
Article
CAS
PubMed
Google Scholar
Weinstabl H, Treu M, Rinnenthal J, Zahn SK, Ettmayer P, Bader G, Dahmann G, Kessler D, Rumpel K, Mischerikow N, et al. Intracellular trapping of the selective phosphoglycerate dehydrogenase (PHGDH) inhibitor BI-4924 Disrupts Serine Biosynthesis. J Med Chem. 2019;62:7976–97.
Article
CAS
PubMed
Google Scholar
Yang JH, Wada A, Yoshida K, Miyoshi Y, Sayano T, Esaki K, Kinoshita MO, Tomonaga S, Azuma N, Watanabe M, et al. Brain-specific Phgdh deletion reveals a pivotal role for L-serine biosynthesis in controlling the level of D-serine, an N-methyl-D-aspartate receptor co-agonist, in adult brain. J Biol Chem. 2010;285:41380–90.
Article
CAS
PubMed
PubMed Central
Google Scholar
Ye J, Fan J, Venneti S, Wan YW, Pawel BR, Zhang J, Finley LW, Lu C, Lindsten T, Cross JR, et al. Serine catabolism regulates mitochondrial redox control during hypoxia. Cancer Discov. 2014;4:1406–17.
Article
CAS
PubMed
PubMed Central
Google Scholar
Ye J, Mancuso A, Tong X, Ward PS, Fan J, Rabinowitz JD, Thompson CB. Pyruvate kinase M2 promotes de novo serine synthesis to sustain mTORC1 activity and cell proliferation. Proc Natl Acad Sci U S A. 2012;109:6904–9.
Article
CAS
PubMed
PubMed Central
Google Scholar
Yoshida K, Furuya S, Osuka S, Mitoma J, Shinoda Y, Watanabe M, Azuma N, Tanaka H, Hashikawa T, Itohara S, et al. Targeted disruption of the mouse 3-phosphoglycerate dehydrogenase gene causes severe neurodevelopmental defects and results in embryonic lethality. J Biol Chem. 2004;279:3573–7.
Article
CAS
PubMed
Google Scholar