{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T13:03:12Z","timestamp":1785416592086,"version":"3.56.0"},"reference-count":66,"publisher":"eLife Sciences Publications, Ltd","license":[{"start":{"date-parts":[[2023,8,4]],"date-time":"2023-08-04T00:00:00Z","timestamp":1691107200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/publicdomain\/zero\/1.0\/"},{"start":{"date-parts":[[2023,8,4]],"date-time":"2023-08-04T00:00:00Z","timestamp":1691107200000},"content-version":"am","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/publicdomain\/zero\/1.0\/"},{"start":{"date-parts":[[2023,8,4]],"date-time":"2023-08-04T00:00:00Z","timestamp":1691107200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/publicdomain\/zero\/1.0\/"}],"funder":[{"DOI":"10.13039\/501100000268","name":"Biotechnology and Biological Sciences Research Council","doi-asserted-by":"publisher","award":["BB\/V006371\/1"],"award-info":[{"award-number":["BB\/V006371\/1"]}],"id":[{"id":"10.13039\/501100000268","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000674","name":"Physiological Society","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000674","id-type":"DOI","asserted-by":"publisher"}]},{"name":"King\u2019s Prize Fellowship"}],"content-domain":{"domain":["elifesciences.org"],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2023,8,3]]},"abstract":"<jats:p>In vertebrates with elongated auditory organs, mechanosensory hair cells (HCs) are organised such that complex sounds are broken down into their component frequencies along a proximal-to-distal long (tonotopic) axis. Acquisition of unique morphologies at the appropriate position along the chick cochlea, the basilar papilla, requires that nascent HCs determine their tonotopic positions during development. The complex signalling within the auditory organ between a developing HC and its local niche along the cochlea is poorly understood. Using a combination of live imaging and NAD(P)H fluorescence lifetime imaging microscopy, we reveal that there is a gradient in the cellular balance between glycolysis and the pentose phosphate pathway in developing HCs along the tonotopic axis. Perturbing this balance by inhibiting different branches of cytosolic glucose catabolism disrupts developmental morphogen signalling and abolishes the normal tonotopic gradient in HC morphology. These findings highlight a causal link between graded morphogen signalling and metabolic reprogramming in specifying the tonotopic identity of developing HCs.<\/jats:p>","DOI":"10.7554\/elife.86233","type":"journal-article","created":{"date-parts":[[2023,8,4]],"date-time":"2023-08-04T07:40:14Z","timestamp":1691134814000},"update-policy":"https:\/\/doi.org\/10.7554\/elife.86233","source":"Crossref","is-referenced-by-count":14,"title":["Gradients of glucose metabolism regulate morphogen signalling required for specifying tonotopic organisation in the chicken cochlea"],"prefix":"10.7554","volume":"12","author":[{"given":"James DB","family":"O'Sullivan","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/0220mzb33","id-type":"ROR","asserted-by":"publisher"}],"name":"Centre for Craniofacial and Regenerative Biology, Faculty of Dentistry Oral and Craniofacial Sciences, King's College London","place":["London, United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8949-6238","authenticated-orcid":true,"given":"Thomas S","family":"Blacker","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/02jx3x895","id-type":"ROR","asserted-by":"publisher"}],"name":"Research Department of Structural and Molecular Biology, University College London","place":["London, United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claire","family":"Scott","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/0220mzb33","id-type":"ROR","asserted-by":"publisher"}],"name":"Centre for Craniofacial and Regenerative Biology, Faculty of Dentistry Oral and Craniofacial Sciences, King's College London","place":["London, United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weise","family":"Chang","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/01cwqze88","id-type":"ROR","asserted-by":"publisher"}],"name":"National Institute on Deafness and Other Communication Disorders, National Institutes of Health","place":["Bethesda, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohi","family":"Ahmed","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/0220mzb33","id-type":"ROR","asserted-by":"publisher"}],"name":"Centre for Craniofacial and Regenerative Biology, Faculty of Dentistry Oral and Craniofacial Sciences, King's College London","place":["London, United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9857-7577","authenticated-orcid":true,"given":"Val","family":"Yianni","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/0220mzb33","id-type":"ROR","asserted-by":"publisher"}],"name":"Centre for Craniofacial and Regenerative Biology, Faculty of Dentistry Oral and Craniofacial Sciences, King's College London","place":["London, United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4916-9574","authenticated-orcid":true,"given":"Zoe F","family":"Mann","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/0220mzb33","id-type":"ROR","asserted-by":"publisher"}],"name":"Centre for Craniofacial and Regenerative Biology, Faculty of Dentistry Oral and Craniofacial Sciences, King's College London","place":["London, United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"4374","published-online":{"date-parts":[[2023,8,4]]},"reference":[{"key":"bib1","doi-asserted-by":"publisher","DOI":"10.3390\/metabo10070285","article-title":"The Pentose Phosphate Pathway Dynamics in Cancer and Its Dependency on Intracellular pH","volume":"10","author":"Alfarouk","year":"2020","journal-title":"Metabolites"},{"key":"bib2","doi-asserted-by":"publisher","first-page":"477","DOI":"10.1038\/s41586-022-04475-w","article-title":"A non-canonical tricarboxylic acid cycle underlies cellular identity","volume":"603","author":"Arnold","year":"2022","journal-title":"Nature"},{"key":"bib3","doi-asserted-by":"publisher","first-page":"2150","DOI":"10.1242\/dev.107011","article-title":"Scaling morphogen gradients during tissue growth by a cell division rule","volume":"141","author":"Averbukh","year":"2014","journal-title":"Development"},{"key":"bib4","doi-asserted-by":"crossref","first-page":"1887","DOI":"10.1016\/S0021-9258(18)64100-6","article-title":"The effects of 2-deoxyglucose on the growth and metabolism of cultured human cells","volume":"236","author":"Barban","year":"1961","journal-title":"The Journal of Biological Chemistry"},{"key":"bib5","doi-asserted-by":"publisher","first-page":"777","DOI":"10.1002\/cne.903140410","article-title":"Appearance and distribution of the 275 kD hair-cell antigen during development of the avian inner ear","volume":"314","author":"Bartolami","year":"1991","journal-title":"The Journal of Comparative Neurology"},{"key":"bib6","doi-asserted-by":"publisher","first-page":"199","DOI":"10.1016\/j.devcel.2020.03.005","article-title":"Metabolic reprogramming promotes neural crest migration via yap\/tead signaling","volume":"53","author":"Bhattacharya","year":"2020","journal-title":"Developmental Cell"},{"key":"bib7","doi-asserted-by":"publisher","first-page":"245","DOI":"10.1016\/j.ydbio.2021.01.018","article-title":"Neural crest metabolism: At the crossroads of development and disease","volume":"475","author":"Bhattacharya","year":"2021","journal-title":"Developmental Biology"},{"key":"bib8","doi-asserted-by":"publisher","first-page":"184","DOI":"10.1016\/j.chemphys.2013.02.019","article-title":"Activated barrier crossing dynamics in the non-radiative decay of NADH and NADPH","volume":"422","author":"Blacker","year":"2013","journal-title":"Chemical Physics"},{"key":"bib9","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms4936","article-title":"Separating NADH and NADPH fluorescence in live cells and tissues using FLIM","volume":"5","author":"Blacker","year":"2014","journal-title":"Nature Communications"},{"key":"bib10","doi-asserted-by":"publisher","first-page":"331","DOI":"10.1016\/j.devcel.2017.01.015","article-title":"Spatiotemporal analysis of a glycolytic activity gradient linked to mouse embryo mesoderm development","volume":"40","author":"Bulusu","year":"2017","journal-title":"Developmental Cell"},{"key":"bib11","doi-asserted-by":"publisher","first-page":"398","DOI":"10.1016\/j.molcel.2018.07.015","article-title":"Metabolic signaling to the nucleus in cancer","volume":"71","author":"Campbell","year":"2018","journal-title":"Molecular Cell"},{"key":"bib12","doi-asserted-by":"publisher","first-page":"9","DOI":"10.1016\/j.devcel.2020.02.015","article-title":"Glycolysis-Independent Glucose Metabolism Distinguishes TE from ICM Fate during Mammalian Embryogenesis","volume":"53","author":"Chi","year":"2020","journal-title":"Developmental Cell"},{"key":"bib13","doi-asserted-by":"publisher","first-page":"181","DOI":"10.1016\/0165-3806(84)90024-5","article-title":"The development of stereociliary bundles in the cochlear duct of chick embryos","volume":"318","author":"Cotanche","year":"1984","journal-title":"Brain Research"},{"key":"bib14","doi-asserted-by":"publisher","first-page":"2489","DOI":"10.1242\/dev.009324","article-title":"Pattern formation in the vertebrate neural tube: a sonic hedgehog morphogen-regulated transcriptional network","volume":"135","author":"Dessaud","year":"2008","journal-title":"Development"},{"key":"bib15","doi-asserted-by":"publisher","first-page":"353","DOI":"10.1016\/s0076-6879(03)61019-0","article-title":"Imaging mitochondrial function in intact cells","volume":"361","author":"Duchen","year":"2003","journal-title":"Methods in Enzymology"},{"key":"bib16","doi-asserted-by":"publisher","first-page":"809","DOI":"10.1146\/annurev.physiol.61.1.809","article-title":"Mechanisms of hair cell tuning","volume":"61","author":"Fettiplace","year":"1999","journal-title":"Annual Review of Physiology"},{"key":"bib17","doi-asserted-by":"publisher","first-page":"11","DOI":"10.1016\/j.heares.2018.11.002","article-title":"Tonotopy in calcium homeostasis and vulnerability of cochlear hair cells","volume":"376","author":"Fettiplace","year":"2019","journal-title":"Hearing Research"},{"key":"bib18","doi-asserted-by":"publisher","first-page":"854","DOI":"10.1007\/BF01186357","article-title":"Freeze fracture analysis of apical membranes in cochlear cultures: differences between basal and apical-coil outer hair cells and effects of neomycin","volume":"22","author":"Forge","year":"1993","journal-title":"Journal of Neurocytology"},{"key":"bib19","doi-asserted-by":"publisher","first-page":"2460","DOI":"10.1523\/JNEUROSCI.08-07-02460.1988","article-title":"Electrical tuning in hair cells isolated from the chick cochlea","volume":"8","author":"Fuchs","year":"1988","journal-title":"The Journal of Neuroscience"},{"key":"bib20","doi-asserted-by":"publisher","first-page":"529","DOI":"10.1113\/jphysiol.1990.sp018271","article-title":"Potassium currents in hair cells isolated from the cochlea of the chick","volume":"429","author":"Fuchs","year":"1990","journal-title":"The Journal of Physiology"},{"key":"bib21","doi-asserted-by":"publisher","first-page":"3165","DOI":"10.1021\/bi00660a001","article-title":"Fluorescence decay studies of reduced nicotinamide adenine dinucleotide in solution and bound to liver alcohol dehydrogenase","volume":"15","author":"Gafni","year":"1976","journal-title":"Biochemistry"},{"key":"bib22","doi-asserted-by":"publisher","first-page":"7013","DOI":"10.1523\/JNEUROSCI.21-18-07013.2001","article-title":"FM1-43 dye behaves as a permeant blocker of the hair-cell mechanotransducer channel","volume":"21","author":"Gale","year":"2001","journal-title":"The Journal of Neuroscience"},{"key":"bib23","doi-asserted-by":"publisher","first-page":"201","DOI":"10.1016\/j.tcb.2019.12.005","article-title":"Metabolic regulation of cell fate and function","volume":"30","author":"Ghosh-Choudhary","year":"2020","journal-title":"Trends in Cell Biology"},{"key":"bib24","doi-asserted-by":"publisher","first-page":"E11010","DOI":"10.1073\/pnas.1713135114","article-title":"Lipid bilayer mediates ion-channel cooperativity in a model of hair-cell mechanotransduction","volume":"114","author":"Gianoli","year":"2017","journal-title":"PNAS"},{"key":"bib25","doi-asserted-by":"publisher","first-page":"595","DOI":"10.1007\/s00114-005-0050-5","article-title":"Audiogram, body mass, and basilar papilla length: correlations in birds and predictions for extinct archosaurs","volume":"92","author":"Gleich","year":"2005","journal-title":"Die Naturwissenschaften"},{"key":"bib26","doi-asserted-by":"publisher","first-page":"6289","DOI":"10.1523\/JNEUROSCI.17-16-06289.1997","article-title":"Pattern formation in the basilar papilla: evidence for cell rearrangement","volume":"17","author":"Goodyear","year":"1997","journal-title":"The Journal of Neuroscience"},{"key":"bib27","doi-asserted-by":"publisher","first-page":"9","DOI":"10.1682\/jrrd.2005.01.0006","article-title":"Hearing loss and aging: new research findings and clinical implications","volume":"42","author":"Gordon-Salant","year":"2005","journal-title":"Journal of Rehabilitation Research and Development"},{"key":"bib28","doi-asserted-by":"publisher","first-page":"415","DOI":"10.1016\/j.cmet.2011.06.017","article-title":"Pyruvate kinase triggers a metabolic feedback loop that controls redox metabolism in respiring cells","volume":"14","author":"Gr\u00fcning","year":"2011","journal-title":"Cell Metabolism"},{"key":"bib29","doi-asserted-by":"publisher","first-page":"309","DOI":"10.1016\/j.neuron.2004.09.020","article-title":"Hair cells require phosphatidylinositol 4,5-bisphosphate for mechanical transduction and adaptation","volume":"44","author":"Hirono","year":"2004","journal-title":"Neuron"},{"key":"bib30","doi-asserted-by":"publisher","first-page":"257","DOI":"10.1006\/jtbi.1999.0955","article-title":"Membranes as possible pacemakers of metabolism","volume":"199","author":"Hulbert","year":"1999","journal-title":"Journal of Theoretical Biology"},{"key":"bib31","doi-asserted-by":"publisher","first-page":"399","DOI":"10.1146\/annurev-cellbio-111315-125134","article-title":"Metabolism and the control of cell fate decisions and stem cell renewal","volume":"32","author":"Ito","year":"2016","journal-title":"Annual Review of Cell and Developmental Biology"},{"key":"bib32","doi-asserted-by":"publisher","first-page":"438","DOI":"10.1002\/dneu.22134","article-title":"The role of Wnt\/\u03b2-catenin signaling in proliferation and regeneration of the developing basilar papilla and lateral line","volume":"74","author":"Jacques","year":"2014","journal-title":"Developmental Neurobiology"},{"key":"bib33","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.56301","article-title":"The Warburg Effect and lactate signaling augment Fgf-MAPK to promote sensory-neural development in the otic vesicle","volume":"9","author":"Kantarci","year":"2020","journal-title":"eLife"},{"key":"bib34","doi-asserted-by":"publisher","first-page":"129","DOI":"10.1002\/cne.902810110","article-title":"Cell production in the chicken cochlea","volume":"281","author":"Katayama","year":"1989","journal-title":"The Journal of Comparative Neurology"},{"key":"bib35","doi-asserted-by":"publisher","first-page":"694","DOI":"10.1038\/nrc.2016.82","article-title":"Metabolic control of epigenetics in cancer","volume":"16","author":"Kinnaird","year":"2016","journal-title":"Nature Reviews. Cancer"},{"key":"bib36","doi-asserted-by":"publisher","first-page":"27","DOI":"10.1002\/bies.201300110","article-title":"Carbohydrate metabolism during vertebrate appendage regeneration: what is its role? How is it regulated?: A postulation that regenerating vertebrate appendages facilitate glycolytic and pentose phosphate pathways to fuel macromolecule biosynthesis","volume":"36","author":"Love","year":"2014","journal-title":"BioEssays"},{"key":"bib37","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms4839","article-title":"A gradient of Bmp7 specifies the tonotopic axis in the developing inner ear","volume":"5","author":"Mann","year":"2014","journal-title":"Nature Communications"},{"key":"bib38","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.83299","article-title":"Glycolytic flux-signaling controls mouse embryo mesoderm development","volume":"11","author":"Miyazawa","year":"2022","journal-title":"eLife"},{"key":"bib39","doi-asserted-by":"publisher","first-page":"17425","DOI":"10.1074\/jbc.RA120.015800","article-title":"Structural basis for allosteric regulation of pyruvate kinase M2 by phosphorylation and acetylation","volume":"295","author":"Nandi","year":"2020","journal-title":"The Journal of Biological Chemistry"},{"key":"bib40","doi-asserted-by":"publisher","first-page":"342","DOI":"10.1016\/j.devcel.2017.02.001","article-title":"A Gradient of Glycolytic Activity Coordinates FGF and Wnt Signaling during Elongation of the Body Axis in Amniote Embryos","volume":"40","author":"Oginuma","year":"2017","journal-title":"Developmental Cell"},{"key":"bib41","doi-asserted-by":"publisher","first-page":"98","DOI":"10.1038\/s41586-020-2428-0","article-title":"Intracellular pH controls WNT downstream of glycolysis in amniote embryos","volume":"584","author":"Oginuma","year":"2020","journal-title":"Nature"},{"key":"bib42","doi-asserted-by":"publisher","DOI":"10.3390\/medicina55060296","article-title":"Alterations of methionine metabolism as potential targets for the prevention and therapy of hepatocellular carcinoma","volume":"55","author":"Pascale","year":"2019","journal-title":"Medicina"},{"key":"bib43","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2022.111552","article-title":"Elevated pentose phosphate pathway flux supports appendage regeneration","volume":"41","author":"Patel","year":"2022","journal-title":"Cell Reports"},{"key":"bib44","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0026289","article-title":"Cholesterol influences voltage-gated calcium channels and BK-type potassium channels in auditory hair cells","volume":"6","author":"Purcell","year":"2011","journal-title":"PLOS ONE"},{"key":"bib45","doi-asserted-by":"publisher","DOI":"10.1186\/s12915-022-01340-0","article-title":"Proton export upregulates aerobic glycolysis","volume":"20","author":"Russell","year":"2022","journal-title":"BMC Biology"},{"key":"bib46","doi-asserted-by":"publisher","DOI":"10.1242\/dev.182154","article-title":"Establishing neuronal diversity in the spinal cord: a time and a place","volume":"146","author":"Sagner","year":"2019","journal-title":"Development"},{"key":"bib47","doi-asserted-by":"publisher","first-page":"19494","DOI":"10.1073\/pnas.0708425104","article-title":"In vivo multiphoton microscopy of NADH and FAD redox states, fluorescence lifetimes, and cellular morphology in precancerous epithelia","volume":"104","author":"Skala","year":"2007","journal-title":"PNAS"},{"key":"bib48","doi-asserted-by":"publisher","first-page":"3746","DOI":"10.1073\/pnas.1417856112","article-title":"Conserved role of Sonic Hedgehog in tonotopic organization of the avian basilar papilla and mammalian cochlea","volume":"112","author":"Son","year":"2015","journal-title":"PNAS"},{"key":"bib49","doi-asserted-by":"publisher","first-page":"927","DOI":"10.1111\/brv.12140","article-title":"The return of metabolism: biochemistry and physiology of the pentose phosphate pathway","volume":"90","author":"Stincone","year":"2015","journal-title":"Biological Reviews of the Cambridge Philosophical Society"},{"key":"bib50","doi-asserted-by":"publisher","first-page":"77","DOI":"10.1016\/0197-0186(86)90103-8","article-title":"Relationship between the pentose-phosphate pathway and the de novo synthesis of fatty acids and cholesterol in oligodendrocyte-enriched glial cultures","volume":"8","author":"Sykes","year":"1986","journal-title":"Neurochemistry International"},{"key":"bib51","doi-asserted-by":"publisher","first-page":"282","DOI":"10.1016\/j.devcel.2020.06.035","article-title":"Exploring the influence of cell metabolism on cell fate through protein post-translational modifications","volume":"54","author":"Tarazona","year":"2020","journal-title":"Developmental Cell"},{"key":"bib52","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms4840","article-title":"Retinoic acid signalling regulates the development of tonotopically patterned hair cells in the chicken cochlea","volume":"5","author":"Thiede","year":"2014","journal-title":"Nature Communications"},{"key":"bib53","doi-asserted-by":"publisher","first-page":"807","DOI":"10.1083\/jcb.96.3.807","article-title":"Actin filaments, stereocilia, and hair cells of the bird cochlea. I. Length, number, width, and distribution of stereocilia of each hair cell are related to the position of the hair cell on the cochlea","volume":"96","author":"Tilney","year":"1983","journal-title":"The Journal of Cell Biology"},{"key":"bib54","doi-asserted-by":"publisher","first-page":"257","DOI":"10.1146\/annurev.cb.08.110192.001353","article-title":"Actin filaments, stereocilia, and hair cells: how cells count and measure","volume":"8","author":"Tilney","year":"1992","journal-title":"Annual Review of Cell Biology"},{"key":"bib55","doi-asserted-by":"publisher","first-page":"181","DOI":"10.1016\/j.ceb.2011.11.005","article-title":"Gradients of signalling in the developing limb","volume":"24","author":"Towers","year":"2012","journal-title":"Current Opinion in Cell Biology"},{"key":"bib56","doi-asserted-by":"publisher","first-page":"1029","DOI":"10.1126\/science.1160809","article-title":"Understanding the Warburg effect: the metabolic requirements of cell proliferation","volume":"324","author":"Vander Heiden","year":"2009","journal-title":"Science"},{"key":"bib57","doi-asserted-by":"publisher","first-page":"2789","DOI":"10.1002\/ijc.24262","article-title":"Modulation of pentose phosphate pathway during cell cycle progression in human colon adenocarcinoma cell line HT29","volume":"124","author":"Viz\u00e1n","year":"2009","journal-title":"International Journal of Cancer"},{"key":"bib58","doi-asserted-by":"publisher","first-page":"6454","DOI":"10.1523\/JNEUROSCI.16-20-06454.1996","article-title":"Sensory organ generation in the chick inner ear","volume":"16","author":"Wu","year":"1996","journal-title":"The Journal of Neuroscience"},{"key":"bib59","doi-asserted-by":"publisher","DOI":"10.1016\/j.redox.2019.101406","article-title":"Noise-induced loss of sensory hair cells is mediated by ROS\/AMPK\u03b1 pathway","volume":"29","author":"Wu","year":"2020","journal-title":"Redox Biology"},{"key":"bib60","doi-asserted-by":"publisher","first-page":"753","DOI":"10.1038\/nprot.2007.76","article-title":"A real-time method of imaging glucose uptake in single, living mammalian cells","volume":"2","author":"Yamada","year":"2007","journal-title":"Nature Protocols"},{"key":"bib61","doi-asserted-by":"publisher","first-page":"1655","DOI":"10.1242\/jcs.166629","article-title":"Pyruvate kinase M2 at a glance","volume":"128","author":"Yang","year":"2015","journal-title":"Journal of Cell Science"},{"key":"bib62","doi-asserted-by":"publisher","first-page":"179","DOI":"10.1089\/ars.2007.1672","article-title":"NAD+\/NADH and NADP+\/NADPH in cellular functions and cell death: regulation and biological consequences","volume":"10","author":"Ying","year":"2008","journal-title":"Antioxidants & Redox Signaling"},{"key":"bib63","doi-asserted-by":"publisher","first-page":"46","DOI":"10.1016\/j.jphotobiol.2008.12.010","article-title":"Two-photon autofluorescence dynamics imaging reveals sensitivity of intracellular NADH concentration and conformation to cell physiology at the single-cell level","volume":"95","author":"Yu","year":"2009","journal-title":"Journal of Photochemistry and Photobiology. B, Biology"},{"key":"bib64","doi-asserted-by":"publisher","DOI":"10.1186\/s13578-019-0317-8","article-title":"PKM2, function and expression and regulation","volume":"9","author":"Zhang","year":"2019","journal-title":"Cell & Bioscience"},{"key":"bib65","doi-asserted-by":"publisher","DOI":"10.1038\/s41420-019-0156-8","article-title":"Low-dose 2-deoxyglucose and metformin synergically inhibit proliferation of human polycystic kidney cells by modulating glucose metabolism","volume":"5","author":"Zhao","year":"2019","journal-title":"Cell Death Discovery"},{"key":"bib66","doi-asserted-by":"publisher","first-page":"37758","DOI":"10.18632\/oncotarget.5386","article-title":"Application of mitochondrial pyruvate carrier blocker UK5099 creates metabolic reprogram and greater stem-like properties in LnCap prostate cancer cells in vitro","volume":"6","author":"Zhong","year":"2015","journal-title":"Oncotarget"}],"container-title":["eLife"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/cdn.elifesciences.org\/articles\/86233\/elife-86233-v2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/cdn.elifesciences.org\/articles\/86233\/elife-86233-v2.xml","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/elifesciences.org\/articles\/86233","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,11]],"date-time":"2023-10-11T21:15:24Z","timestamp":1697058924000},"score":1,"resource":{"primary":{"URL":"https:\/\/elifesciences.org\/articles\/86233"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,8,4]]},"references-count":66,"alternative-id":["10.7554\/eLife.86233"],"URL":"https:\/\/doi.org\/10.7554\/elife.86233","archive":["CLOCKSS"],"relation":{"has-preprint":[{"id-type":"doi","id":"10.1101\/2022.04.11.487851","asserted-by":"subject"},{"id-type":"doi","id":"10.1101\/2022.04.11.487851","asserted-by":"object"}],"has-review":[{"id-type":"doi","id":"10.7554\/eLife.86233.sa0","asserted-by":"object"},{"id-type":"doi","id":"10.7554\/eLife.86233.sa1","asserted-by":"object"},{"id-type":"doi","id":"10.7554\/eLife.86233.sa2","asserted-by":"object"}]},"ISSN":["2050-084X"],"issn-type":[{"value":"2050-084X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,8,4]]},"assertion":[{"value":"single anonymised","name":"peer_review_transparency","label":"Peer review transparency","group":{"name":"peer_review_taxonomy"}},{"value":"other reviewer(s), editor","name":"peer_review_interaction","label":"Peer review interaction","group":{"name":"peer_review_taxonomy"}},{"value":"review summaries, review reports, author\/editor communication, reviewer identities reviewer opt in, editor identities","name":"peer_review_published","label":"Peer review published","group":{"name":"peer_review_taxonomy"}},{"value":"open (sign in with ORCID iD required)","name":"post_publication_commenting","label":"Post publication commenting","group":{"name":"post_publication_commenting"}}],"article-number":"e86233"}}