Export Ready — 

Dichloroacetate, the Pyruvate Dehydrogenase Complex and the Modulation of mESC Pluripotency

Bibliographic Details
Main Author: Rodrigues, Ana Sofia
Publication Date: 2015
Other Authors: Correia, Marcelo, Gomes, Andreia, Pereira, Sandro L., Perestrelo, Tânia, Sousa, Maria Inês, Ramalho-Santos, João
Format: Article
Language: eng
Source: Repositórios Científicos de Acesso Aberto de Portugal (RCAAP)
Download full: https://hdl.handle.net/10316/109269
https://doi.org/10.1371/journal.pone.0131663
Summary: The pyruvate dehydrogenase (PDH) complex is localized in the mitochondrial matrix catalyzing the irreversible decarboxylation of pyruvate to acetyl-CoA and NADH. For proper complex regulation the E1-α subunit functions as an on/off switch regulated by phosphorylation/dephosphorylation. In different cell types one of the four-pyruvate dehydrogenase kinase isoforms (PDHK1-4) can phosphorylate this subunit leading to PDH inactivation. Our previous results with human Embryonic Stem Cells (hESC), suggested that PDHK could be a key regulator in the metabolic profile of pluripotent cells, as it is upregulated in pluripotent stem cells. Therefore, we wondered if metabolic modulation, via inexpensive pharmacological inhibition of PDHK, could impact metabolism and pluripotency.
id RCAP_83795337752c8eecfd2bcb018df49957
oai_identifier_str oai:estudogeral.uc.pt:10316/109269
network_acronym_str RCAP
network_name_str Repositórios Científicos de Acesso Aberto de Portugal (RCAAP)
repository_id_str https://opendoar.ac.uk/repository/7160
spelling Dichloroacetate, the Pyruvate Dehydrogenase Complex and the Modulation of mESC PluripotencyAnimalsCell LineCell ProliferationDichloroacetic AcidEmbryonic Stem CellsGlycolysisMiceOxidative PhosphorylationPluripotent Stem CellsPyruvate Dehydrogenase ComplexThe pyruvate dehydrogenase (PDH) complex is localized in the mitochondrial matrix catalyzing the irreversible decarboxylation of pyruvate to acetyl-CoA and NADH. For proper complex regulation the E1-α subunit functions as an on/off switch regulated by phosphorylation/dephosphorylation. In different cell types one of the four-pyruvate dehydrogenase kinase isoforms (PDHK1-4) can phosphorylate this subunit leading to PDH inactivation. Our previous results with human Embryonic Stem Cells (hESC), suggested that PDHK could be a key regulator in the metabolic profile of pluripotent cells, as it is upregulated in pluripotent stem cells. Therefore, we wondered if metabolic modulation, via inexpensive pharmacological inhibition of PDHK, could impact metabolism and pluripotency.The authors thank Fundação para a Ciência e a Tecnologia (FCT) Portugal for grant support (PTDC/EBB-EBI/ 120634/2010 and PDTC/ QUI-BIQ/120652/2010 co-funded by Compete/ FEDER/National Funds; and scholarships attributed to ASR (SFRH/BD/33463/2008); to MC (SFRH/BD/ 51681/2011), to TP (SFRH/BD/51684/2011), AG (SFRH/BD/51968/2012) and SLP (SFRH/BPD/98995/ 2013) and also to QREN (Centro-01-0762-FEDER- 00204). Center for Neuroscience and Cell Biology (CNC) funding is also supported by FCT (PEst-C/ SAU/LA0001/2011).Public Library of Science2015info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articlehttps://hdl.handle.net/10316/109269https://hdl.handle.net/10316/109269https://doi.org/10.1371/journal.pone.0131663eng1932-6203Rodrigues, Ana SofiaCorreia, MarceloGomes, AndreiaPereira, Sandro L.Perestrelo, TâniaSousa, Maria InêsRamalho-Santos, Joãoinfo:eu-repo/semantics/openAccessreponame:Repositórios Científicos de Acesso Aberto de Portugal (RCAAP)instname:FCCN, serviços digitais da FCT – Fundação para a Ciência e a Tecnologiainstacron:RCAAP2024-09-26T15:43:54Zoai:estudogeral.uc.pt:10316/109269Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireinfo@rcaap.ptopendoar:https://opendoar.ac.uk/repository/71602025-05-29T06:00:55.934884Repositórios Científicos de Acesso Aberto de Portugal (RCAAP) - FCCN, serviços digitais da FCT – Fundação para a Ciência e a Tecnologiafalse
dc.title.none.fl_str_mv Dichloroacetate, the Pyruvate Dehydrogenase Complex and the Modulation of mESC Pluripotency
title Dichloroacetate, the Pyruvate Dehydrogenase Complex and the Modulation of mESC Pluripotency
spellingShingle Dichloroacetate, the Pyruvate Dehydrogenase Complex and the Modulation of mESC Pluripotency
Rodrigues, Ana Sofia
Animals
Cell Line
Cell Proliferation
Dichloroacetic Acid
Embryonic Stem Cells
Glycolysis
Mice
Oxidative Phosphorylation
Pluripotent Stem Cells
Pyruvate Dehydrogenase Complex
title_short Dichloroacetate, the Pyruvate Dehydrogenase Complex and the Modulation of mESC Pluripotency
title_full Dichloroacetate, the Pyruvate Dehydrogenase Complex and the Modulation of mESC Pluripotency
title_fullStr Dichloroacetate, the Pyruvate Dehydrogenase Complex and the Modulation of mESC Pluripotency
title_full_unstemmed Dichloroacetate, the Pyruvate Dehydrogenase Complex and the Modulation of mESC Pluripotency
title_sort Dichloroacetate, the Pyruvate Dehydrogenase Complex and the Modulation of mESC Pluripotency
author Rodrigues, Ana Sofia
author_facet Rodrigues, Ana Sofia
Correia, Marcelo
Gomes, Andreia
Pereira, Sandro L.
Perestrelo, Tânia
Sousa, Maria Inês
Ramalho-Santos, João
author_role author
author2 Correia, Marcelo
Gomes, Andreia
Pereira, Sandro L.
Perestrelo, Tânia
Sousa, Maria Inês
Ramalho-Santos, João
author2_role author
author
author
author
author
author
dc.contributor.author.fl_str_mv Rodrigues, Ana Sofia
Correia, Marcelo
Gomes, Andreia
Pereira, Sandro L.
Perestrelo, Tânia
Sousa, Maria Inês
Ramalho-Santos, João
dc.subject.por.fl_str_mv Animals
Cell Line
Cell Proliferation
Dichloroacetic Acid
Embryonic Stem Cells
Glycolysis
Mice
Oxidative Phosphorylation
Pluripotent Stem Cells
Pyruvate Dehydrogenase Complex
topic Animals
Cell Line
Cell Proliferation
Dichloroacetic Acid
Embryonic Stem Cells
Glycolysis
Mice
Oxidative Phosphorylation
Pluripotent Stem Cells
Pyruvate Dehydrogenase Complex
description The pyruvate dehydrogenase (PDH) complex is localized in the mitochondrial matrix catalyzing the irreversible decarboxylation of pyruvate to acetyl-CoA and NADH. For proper complex regulation the E1-α subunit functions as an on/off switch regulated by phosphorylation/dephosphorylation. In different cell types one of the four-pyruvate dehydrogenase kinase isoforms (PDHK1-4) can phosphorylate this subunit leading to PDH inactivation. Our previous results with human Embryonic Stem Cells (hESC), suggested that PDHK could be a key regulator in the metabolic profile of pluripotent cells, as it is upregulated in pluripotent stem cells. Therefore, we wondered if metabolic modulation, via inexpensive pharmacological inhibition of PDHK, could impact metabolism and pluripotency.
publishDate 2015
dc.date.none.fl_str_mv 2015
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
dc.type.driver.fl_str_mv info:eu-repo/semantics/article
format article
status_str publishedVersion
dc.identifier.uri.fl_str_mv https://hdl.handle.net/10316/109269
https://hdl.handle.net/10316/109269
https://doi.org/10.1371/journal.pone.0131663
url https://hdl.handle.net/10316/109269
https://doi.org/10.1371/journal.pone.0131663
dc.language.iso.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv 1932-6203
dc.rights.driver.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.publisher.none.fl_str_mv Public Library of Science
publisher.none.fl_str_mv Public Library of Science
dc.source.none.fl_str_mv reponame:Repositórios Científicos de Acesso Aberto de Portugal (RCAAP)
instname:FCCN, serviços digitais da FCT – Fundação para a Ciência e a Tecnologia
instacron:RCAAP
instname_str FCCN, serviços digitais da FCT – Fundação para a Ciência e a Tecnologia
instacron_str RCAAP
institution RCAAP
reponame_str Repositórios Científicos de Acesso Aberto de Portugal (RCAAP)
collection Repositórios Científicos de Acesso Aberto de Portugal (RCAAP)
repository.name.fl_str_mv Repositórios Científicos de Acesso Aberto de Portugal (RCAAP) - FCCN, serviços digitais da FCT – Fundação para a Ciência e a Tecnologia
repository.mail.fl_str_mv info@rcaap.pt
_version_ 1833602548024475648

Similar Items