{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,11]],"date-time":"2026-05-11T19:23:35Z","timestamp":1778527415408,"version":"3.51.4"},"reference-count":57,"publisher":"Public Library of Science (PLoS)","issue":"6","license":[{"start":{"date-parts":[[2011,6,17]],"date-time":"2011-06-17T00:00:00Z","timestamp":1308268800000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"DOI":"10.1371\/journal.pone.0020914","type":"journal-article","created":{"date-parts":[[2011,6,18]],"date-time":"2011-06-18T01:56:33Z","timestamp":1308362193000},"page":"e20914","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":596,"title":["Energy Metabolism in Human Pluripotent Stem Cells and Their Differentiated Counterparts"],"prefix":"10.1371","volume":"6","author":[{"given":"Sandra","family":"Varum","sequence":"first","affiliation":[]},{"given":"Ana S.","family":"Rodrigues","sequence":"additional","affiliation":[]},{"given":"Michelle B.","family":"Moura","sequence":"additional","affiliation":[]},{"given":"Olga","family":"Momcilovic","sequence":"additional","affiliation":[]},{"given":"Charles A.","family":"Easley","sequence":"additional","affiliation":[]},{"given":"Jo\u00e3o","family":"Ramalho-Santos","sequence":"additional","affiliation":[]},{"given":"Bennett","family":"Van Houten","sequence":"additional","affiliation":[]},{"given":"Gerald","family":"Schatten","sequence":"additional","affiliation":[]}],"member":"340","published-online":{"date-parts":[[2011,6,17]]},"reference":[{"key":"ref1","doi-asserted-by":"crossref","first-page":"1917","DOI":"10.1126\/science.1151526","article-title":"Induced pluripotent stem cell lines derived from human somatic cells.","volume":"318","author":"J Yu","year":"2007","journal-title":"Science"},{"key":"ref2","doi-asserted-by":"crossref","first-page":"663","DOI":"10.1016\/j.cell.2006.07.024","article-title":"Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors.","volume":"126","author":"K Takahashi","year":"2006","journal-title":"Cell"},{"key":"ref3","doi-asserted-by":"crossref","first-page":"861","DOI":"10.1016\/j.cell.2007.11.019","article-title":"Induction of pluripotent stem cells from adult human fibroblasts by defined factors.","volume":"131","author":"K Takahashi","year":"2007","journal-title":"Cell"},{"key":"ref4","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1016\/j.stem.2009.06.008","article-title":"Induced pluripotent stem cells and embryonic stem cells are distinguished by gene expression signatures.","volume":"5","author":"MH Chin","year":"2009","journal-title":"Cell Stem Cell"},{"key":"ref5","first-page":"55","article-title":"Directly reprogrammed fibroblasts show global epigenetic remodeling and widespread tissue contribution.","volume":"1","author":"N Maherali","year":"2007","journal-title":"Cell Stem Cell"},{"key":"ref6","doi-asserted-by":"crossref","first-page":"1350","DOI":"10.1038\/ng.471","article-title":"Differential methylation of tissue- and cancer-specific CpG island shores distinguishes human induced pluripotent stem cells, embryonic stem cells and fibroblasts.","volume":"41","author":"A Doi","year":"2009","journal-title":"Nat Genet"},{"key":"ref7","doi-asserted-by":"crossref","first-page":"479","DOI":"10.1016\/j.stem.2010.03.018","article-title":"Distinct epigenomic landscapes of pluripotent and lineage-committed human cells.","volume":"6","author":"RD Hawkins","year":"2010","journal-title":"Cell Stem Cell"},{"key":"ref8","doi-asserted-by":"crossref","first-page":"353","DOI":"10.1038\/nbt.1530","article-title":"Targeted bisulfite sequencing reveals changes in DNA methylation associated with nuclear reprogramming.","volume":"27","author":"J Deng","year":"2009","journal-title":"Nat Biotechnol"},{"key":"ref9","doi-asserted-by":"crossref","first-page":"68","DOI":"10.1038\/nature09798","article-title":"Hotspots of aberrant epigenomic reprogramming in human induced pluripotent stem cells.","volume":"471","author":"R Lister","year":"2011","journal-title":"Nature"},{"key":"ref10","doi-asserted-by":"crossref","first-page":"439","DOI":"10.1016\/j.cell.2010.12.032","article-title":"Reference Maps of human ES and iPS cell variation enable high-throughput characterization of pluripotent cell lines.","volume":"144","author":"C Bock","year":"2011","journal-title":"Cell"},{"key":"ref11","doi-asserted-by":"crossref","first-page":"58","DOI":"10.1038\/nature09871","article-title":"Copy number variation and selection during reprogramming to pluripotency.","volume":"471","author":"SM Hussein","year":"2011","journal-title":"Nature"},{"key":"ref12","doi-asserted-by":"crossref","first-page":"673","DOI":"10.1530\/jrf.0.0990673","article-title":"Oxygen tension in the oviduct and uterus of rhesus monkeys, hamsters and rabbits.","volume":"99","author":"B Fischer","year":"1993","journal-title":"J Reprod Fertil"},{"key":"ref13","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1038\/nature09805","article-title":"Somatic coding mutations in human induced pluripotent stem cells.","volume":"471","author":"A Gore","year":"2011","journal-title":"Nature"},{"key":"ref14","doi-asserted-by":"crossref","DOI":"10.1038\/nature10135","article-title":"Immunogenicity of induced pluripotent stem cells.","author":"T Zhao","year":"2011"},{"key":"ref15","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1530\/jrf.0.0720009","article-title":"Pyruvate and glucose uptake by mouse ova and preimplantation embryos.","volume":"72","author":"HJ Leese","year":"1984","journal-title":"J Reprod Fertil"},{"key":"ref16","doi-asserted-by":"crossref","first-page":"553","DOI":"10.1093\/humupd\/dmp016","article-title":"Mitochondrial functionality in reproduction: from gonads and gametes to embryos and embryonic stem cells.","volume":"15","author":"J Ramalho-Santos","year":"2009","journal-title":"Hum Reprod Update"},{"key":"ref17","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1002\/jez.1401760206","article-title":"Mitochondria and early development of the mouse.","volume":"176","author":"S Stern","year":"1971","journal-title":"J Exp Zool"},{"key":"ref18","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1111\/j.1432-0436.2006.00052.x","article-title":"Energy metabolism of the inner cell mass and trophectoderm of the mouse blastocyst.","volume":"74","author":"FD Houghton","year":"2006","journal-title":"Differentiation"},{"key":"ref19","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1089\/clo.2005.7.141","article-title":"The expression of mitochondrial DNA transcription factors during early cardiomyocyte in vitro differentiation from human embryonic stem cells.","volume":"7","author":"JC St John","year":"2005","journal-title":"Cloning Stem Cells"},{"key":"ref20","doi-asserted-by":"crossref","first-page":"1472","DOI":"10.1016\/j.bbrc.2006.08.020","article-title":"Dynamic changes in mitochondrial biogenesis and antioxidant enzymes during the spontaneous differentiation of human embryonic stem cells.","volume":"348","author":"YM Cho","year":"2006","journal-title":"Biochem Biophys Res Commun"},{"key":"ref21","doi-asserted-by":"crossref","first-page":"721","DOI":"10.1002\/stem.404","article-title":"The senescence-related mitochondrial\/oxidative stress pathway is repressed in human induced pluripotent stem cells.","volume":"28","author":"A Prigione","year":"2010","journal-title":"Stem Cells"},{"key":"ref22","doi-asserted-by":"crossref","first-page":"4783","DOI":"10.1073\/pnas.0501283102","article-title":"Low O2 tensions and the prevention of differentiation of hES cells.","volume":"102","author":"T Ezashi","year":"2005","journal-title":"Proc Natl Acad Sci U S A"},{"key":"ref23","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1530\/REP-09-0300","article-title":"Hypoxia inducible factors regulate pluripotency and proliferation in human embryonic stem cells cultured at reduced oxygen tensions.","volume":"139","author":"CE Forristal","year":"2010","journal-title":"Reproduction"},{"key":"ref24","doi-asserted-by":"crossref","first-page":"237","DOI":"10.1016\/j.stem.2009.08.001","article-title":"Hypoxia enhances the generation of induced pluripotent stem cells.","volume":"5","author":"Y Yoshida","year":"2009","journal-title":"Cell Stem Cell"},{"key":"ref25","doi-asserted-by":"crossref","first-page":"62","DOI":"10.1126\/science.1147949","article-title":"Life with oxygen.","volume":"318","author":"GL Semenza","year":"2007","journal-title":"Science"},{"key":"ref26","doi-asserted-by":"crossref","first-page":"3735","DOI":"10.1073\/pnas.74.9.3735","article-title":"High aerobic glycolysis of rat hepatoma cells in culture: role of mitochondrial hexokinase.","volume":"74","author":"E Bustamante","year":"1977","journal-title":"Proc Natl Acad Sci U S A"},{"key":"ref27","doi-asserted-by":"crossref","first-page":"8699","DOI":"10.1016\/S0021-9258(19)68900-3","article-title":"Energy metabolism of tumor cells. Requirement for a form of hexokinase with a propensity for mitochondrial binding.","volume":"256","author":"E Bustamante","year":"1981","journal-title":"J Biol Chem"},{"key":"ref28","doi-asserted-by":"crossref","first-page":"1143","DOI":"10.1042\/bst0311143","article-title":"Regulation of pyruvate dehydrogenase complex activity by reversible phosphorylation.","volume":"31","author":"MJ Holness","year":"2003","journal-title":"Biochem Soc Trans"},{"key":"ref29","doi-asserted-by":"crossref","first-page":"830","DOI":"10.1007\/s00018-007-6380-z","article-title":"Pyruvate dehydrogenase kinase regulatory mechanisms and inhibition in treating diabetes, heart ischemia, and cancer.","volume":"64","author":"TE Roche","year":"2007","journal-title":"Cell Mol Life Sci"},{"key":"ref30","doi-asserted-by":"crossref","first-page":"372","DOI":"10.1016\/j.yexmp.2010.08.006","article-title":"Cancer metabolism: the Warburg effect today.","volume":"89","author":"LM Ferreira","year":"2010","journal-title":"Exp Mol Pathol"},{"key":"ref31","doi-asserted-by":"crossref","first-page":"4382","DOI":"10.1073\/pnas.1014519107","article-title":"Hypoxia and lineage specification of cell line-derived colorectal cancer stem cells.","volume":"108","author":"TM Yeung","year":"2011","journal-title":"Proc Natl Acad Sci U S A"},{"key":"ref32","doi-asserted-by":"crossref","first-page":"1746","DOI":"10.1038\/sj.bjc.6605701","article-title":"Dichloroacetate induces apoptosis and cell-cycle arrest in colorectal cancer cells.","volume":"102","author":"BM Madhok","year":"2010","journal-title":"Br J Cancer"},{"key":"ref33","doi-asserted-by":"crossref","first-page":"733","DOI":"10.1002\/mc.20539","article-title":"Mitochondrial bioenergetic background confers a survival advantage to HepG2 cells in response to chemotherapy.","volume":"48","author":"D Loiseau","year":"2009","journal-title":"Mol Carcinog"},{"key":"ref34","article-title":"Choosing between glycolysis and oxidative phosphorylation: A tumor&apos;s dilemma?","author":"C Jose","year":"2010"},{"key":"ref35","doi-asserted-by":"crossref","first-page":"142","DOI":"10.1016\/j.scr.2009.07.002","article-title":"Enhancement of human embryonic stem cell pluripotency through inhibition of the mitochondrial respiratory chain.","volume":"3","author":"S Varum","year":"2009","journal-title":"Stem Cell Res"},{"key":"ref36","doi-asserted-by":"crossref","first-page":"1582","DOI":"10.1038\/nprot.2009.151","article-title":"Isolation of mitochondria-associated membranes and mitochondria from animal tissues and cells.","volume":"4","author":"MR Wieckowski","year":"2009","journal-title":"Nat Protoc"},{"key":"ref37","doi-asserted-by":"crossref","first-page":"452","DOI":"10.1016\/j.ymeth.2010.03.006","article-title":"Alterations in bioenergetics due to changes in mitochondrial DNA copy number.","volume":"51","author":"W Qian","year":"2010","journal-title":"Methods"},{"key":"ref38","doi-asserted-by":"crossref","first-page":"39414","DOI":"10.1074\/jbc.M406576200","article-title":"Inhibitors of the quinone-binding site allow rapid superoxide production from mitochondrial NADH:ubiquinone oxidoreductase (complex I).","volume":"279","author":"AJ Lambert","year":"2004","journal-title":"J Biol Chem"},{"key":"ref39","doi-asserted-by":"crossref","first-page":"17422","DOI":"10.1016\/S0021-9258(19)77853-3","article-title":"Functional significance of mitochondrial bound hexokinase in tumor cell metabolism. Evidence for preferential phosphorylation of glucose by intramitochondrially generated ATP.","volume":"263","author":"KK Arora","year":"1988","journal-title":"J Biol Chem"},{"key":"ref40","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1016\/j.semcancer.2008.11.006","article-title":"Hexokinase-2 bound to mitochondria: cancer&apos;s stygian link to the &quot;Warburg Effect&quot; and a pivotal target for effective therapy.","volume":"19","author":"SP Mathupala","year":"2009","journal-title":"Semin Cancer Biol"},{"key":"ref41","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1016\/j.jchromb.2005.01.001","article-title":"Quantification of sugar phosphate intermediates of the pentose phosphate pathway by LC-MS\/MS: application to two new inherited defects of metabolism.","volume":"823","author":"MM Wamelink","year":"2005","journal-title":"J Chromatogr B Analyt Technol Biomed Life Sci"},{"key":"ref42","doi-asserted-by":"crossref","first-page":"174","DOI":"10.1096\/fasebj.8.2.8119488","article-title":"Glucose-6-phosphate dehydrogenase: a &quot;housekeeping&quot; enzyme subject to tissue-specific regulation by hormones, nutrients, and oxidant stress.","volume":"8","author":"RF Kletzien","year":"1994","journal-title":"FASEB J"},{"key":"ref43","doi-asserted-by":"crossref","first-page":"10609","DOI":"10.1074\/jbc.273.17.10609","article-title":"Importance of glucose-6-phosphate dehydrogenase activity for cell growth.","volume":"273","author":"WN Tian","year":"1998","journal-title":"J Biol Chem"},{"key":"ref44","first-page":"1183","article-title":"Transforming growth factor beta2 promotes glucose carbon incorporation into nucleic acid ribose through the nonoxidative pentose cycle in lung epithelial carcinoma cells.","volume":"60","author":"LG Boros","year":"2000","journal-title":"Cancer Res"},{"key":"ref45","doi-asserted-by":"crossref","first-page":"150","DOI":"10.1207\/S15327914NC3602_2","article-title":"Role of thiamin (vitamin B-1) and transketolase in tumor cell proliferation.","volume":"36","author":"M Cascante","year":"2000","journal-title":"Nutr Cancer"},{"key":"ref46","doi-asserted-by":"crossref","first-page":"5923","DOI":"10.1128\/MCB.24.13.5923-5936.2004","article-title":"Evaluation of myc E-box phylogenetic footprints in glycolytic genes by chromatin immunoprecipitation assays.","volume":"24","author":"JW Kim","year":"2004","journal-title":"Mol Cell Biol"},{"key":"ref47","doi-asserted-by":"crossref","first-page":"108","DOI":"10.1016\/j.ccr.2007.07.006","article-title":"HIF and c-Myc: sibling rivals for control of cancer cell metabolism and proliferation.","volume":"12","author":"JD Gordan","year":"2007","journal-title":"Cancer Cell"},{"key":"ref48","doi-asserted-by":"crossref","first-page":"6225","DOI":"10.1128\/MCB.25.14.6225-6234.2005","article-title":"Myc stimulates nuclearly encoded mitochondrial genes and mitochondrial biogenesis.","volume":"25","author":"F Li","year":"2005","journal-title":"Mol Cell Biol"},{"key":"ref49","doi-asserted-by":"crossref","first-page":"676","DOI":"10.1126\/science.283.5402.676","article-title":"Coordinated regulation of iron-controlling genes, H-ferritin and IRP2, by c-MYC.","volume":"283","author":"KJ Wu","year":"1999","journal-title":"Science"},{"key":"ref50","doi-asserted-by":"crossref","first-page":"837","DOI":"10.1016\/S0022-3476(71)80356-6","article-title":"The disappearance of fetal lung fluid following birth.","volume":"78","author":"FH Adams","year":"1971","journal-title":"J Pediatr"},{"key":"ref51","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1186\/1471-213X-8-57","article-title":"Expression profiling in transgenic FVB\/N embryonic stem cells overexpressing STAT3.","volume":"8","author":"P Cinelli","year":"2008","journal-title":"BMC Dev Biol"},{"key":"ref52","doi-asserted-by":"crossref","first-page":"22517","DOI":"10.1074\/jbc.274.32.22517","article-title":"Hexokinase II-deficient mice. Prenatal death of homozygotes without disturbances in glucose tolerance in heterozygotes.","volume":"274","author":"S Heikkinen","year":"1999","journal-title":"J Biol Chem"},{"key":"ref53","doi-asserted-by":"crossref","first-page":"331","DOI":"10.1023\/A:1022442629543","article-title":"Hexokinase binding to mitochondria: a basis for proliferative energy metabolism.","volume":"29","author":"SG Golshani-Hebroni","year":"1997","journal-title":"J Bioenerg Biomembr"},{"key":"ref54","doi-asserted-by":"crossref","first-page":"730","DOI":"10.1128\/MCB.24.2.730-740.2004","article-title":"Akt inhibits apoptosis downstream of BID cleavage via a glucose-dependent mechanism involving mitochondrial hexokinases.","volume":"24","author":"N Majewski","year":"2004","journal-title":"Mol Cell Biol"},{"key":"ref55","doi-asserted-by":"crossref","first-page":"13842","DOI":"10.1073\/pnas.0913834107","article-title":"RNAi screen for telomerase reverse transcriptase transcriptional regulators identifies HIF1alpha as critical for telomerase function in murine embryonic stem cells.","volume":"107","author":"M Coussens","year":"2010","journal-title":"Proc Natl Acad Sci U S A"},{"key":"ref56","doi-asserted-by":"crossref","first-page":"584","DOI":"10.1016\/j.mito.2010.08.002","article-title":"Metabolic flexibility and cell hierarchy in metastatic cancer.","volume":"10","author":"MV Berridge","year":"2010","journal-title":"Mitochondrion"},{"key":"ref57","doi-asserted-by":"crossref","first-page":"e14095","DOI":"10.1371\/journal.pone.0014095","article-title":"Mitochondrial rejuvenation after induced pluripotency.","volume":"5","author":"ST Suhr","year":"2010","journal-title":"PLoS One"}],"container-title":["PLoS ONE"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/dx.plos.org\/10.1371\/journal.pone.0020914","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,11,25]],"date-time":"2021-11-25T19:51:56Z","timestamp":1637869916000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0020914"}},"subtitle":[],"editor":[{"given":"Marian","family":"Ludgate","sequence":"first","affiliation":[]}],"short-title":[],"issued":{"date-parts":[[2011,6,17]]},"references-count":57,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2011,6,17]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0020914","relation":{},"ISSN":["1932-6203"],"issn-type":[{"value":"1932-6203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2011,6,17]]}}}