Metformin regulates global DNA methylation via mitochondrial one-carbon metabolism.
Identifieur interne : 000806 ( Main/Exploration ); précédent : 000805; suivant : 000807Metformin regulates global DNA methylation via mitochondrial one-carbon metabolism.
Auteurs : E. Cuyàs [Espagne] ; S. Fernández-Arroyo [Espagne] ; S. Verdura [Espagne] ; R F García [Espagne] ; J. Stursa [République tchèque] ; L. Werner [République tchèque] ; E. Blanco-González [Espagne] ; M. Montes-Bay N [Espagne] ; J. Joven [Espagne] ; B. Viollet [France] ; J. Neuzil [République tchèque] ; J A Menendez [Espagne]Source :
- Oncogene [ 1476-5594 ] ; 2017.
Abstract
The anti-diabetic biguanide metformin may exert health-promoting effects via metabolic regulation of the epigenome. Here we show that metformin promotes global DNA methylation in non-cancerous, cancer-prone and metastatic cancer cells by decreasing S-adenosylhomocysteine (SAH), a strong feedback inhibitor of S-adenosylmethionine (SAM)-dependent DNA methyltransferases, while promoting the accumulation of SAM, the universal methyl donor for cellular methylation. Using metformin and a mitochondria/complex I (mCI)-targeted analog of metformin (norMitoMet) in experimental pairs of wild-type and AMP-activated protein kinase (AMPK)-, serine hydroxymethyltransferase 2 (SHMT2)- and mCI-null cells, we provide evidence that metformin increases the SAM:SAH ratio-related methylation capacity by targeting the coupling between serine mitochondrial one-carbon flux and CI activity. By increasing the contribution of one-carbon units to the SAM from folate stores while decreasing SAH in response to AMPK-sensed energetic crisis, metformin can operate as a metabolo-epigenetic regulator capable of reprogramming one of the key conduits linking cellular metabolism to the DNA methylation machinery.Oncogene advance online publication, 23 October 2017; doi:10.1038/onc.2017.367.
DOI: 10.1038/onc.2017.367
PubMed: 29059169
Affiliations:
Links toward previous steps (curation, corpus...)
- to stream PubMed, to step Corpus: 000245
- to stream PubMed, to step Curation: 000244
- to stream PubMed, to step Checkpoint: 000244
- to stream Ncbi, to step Merge: 005083
- to stream Ncbi, to step Curation: 005083
- to stream Ncbi, to step Checkpoint: 005083
- to stream Main, to step Merge: 000801
- to stream Main, to step Curation: 000806
Le document en format XML
<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Metformin regulates global DNA methylation via mitochondrial one-carbon metabolism.</title><author><name sortKey="Cuyas, E" sort="Cuyas, E" uniqKey="Cuyas E" first="E" last="Cuyàs">E. Cuyàs</name><affiliation wicri:level="1"><nlm:affiliation>ProCURE (Program Against Cancer Therapeutic Resistance), Metabolism & Cancer Group, Catalan Institute of Oncology, Girona, Catalonia, Spain.</nlm:affiliation><country xml:lang="fr">Espagne</country><wicri:regionArea>ProCURE (Program Against Cancer Therapeutic Resistance), Metabolism & Cancer Group, Catalan Institute of Oncology, Girona, Catalonia</wicri:regionArea><wicri:noRegion>Catalonia</wicri:noRegion></affiliation></author><author><name sortKey="Fernandez Arroyo, S" sort="Fernandez Arroyo, S" uniqKey="Fernandez Arroyo S" first="S" last="Fernández-Arroyo">S. Fernández-Arroyo</name><affiliation wicri:level="1"><nlm:affiliation>Unitat de Recerca Biomèdica, Hospital Universitari Sant Joan, Institut d'Investigació Sanitària Pere Virgili, Universitat Rovira i Virgili, Reus, Spain.</nlm:affiliation><country xml:lang="fr">Espagne</country><wicri:regionArea>Unitat de Recerca Biomèdica, Hospital Universitari Sant Joan, Institut d'Investigació Sanitària Pere Virgili, Universitat Rovira i Virgili, Reus</wicri:regionArea><wicri:noRegion>Reus</wicri:noRegion></affiliation></author><author><name sortKey="Verdura, S" sort="Verdura, S" uniqKey="Verdura S" first="S" last="Verdura">S. Verdura</name><affiliation wicri:level="1"><nlm:affiliation>ProCURE (Program Against Cancer Therapeutic Resistance), Metabolism & Cancer Group, Catalan Institute of Oncology, Girona, Catalonia, Spain.</nlm:affiliation><country xml:lang="fr">Espagne</country><wicri:regionArea>ProCURE (Program Against Cancer Therapeutic Resistance), Metabolism & Cancer Group, Catalan Institute of Oncology, Girona, Catalonia</wicri:regionArea><wicri:noRegion>Catalonia</wicri:noRegion></affiliation></author><author><name sortKey="Garcia, R F" sort="Garcia, R F" uniqKey="Garcia R" first="R F" last="García">R F García</name><affiliation wicri:level="1"><nlm:affiliation>Department of Physical and Analytical Chemistry, Faculty of Chemistry, University of Oviedo, Oviedo, Spain.</nlm:affiliation><country xml:lang="fr">Espagne</country><wicri:regionArea>Department of Physical and Analytical Chemistry, Faculty of Chemistry, University of Oviedo, Oviedo</wicri:regionArea><wicri:noRegion>Oviedo</wicri:noRegion></affiliation></author><author><name sortKey="Stursa, J" sort="Stursa, J" uniqKey="Stursa J" first="J" last="Stursa">J. Stursa</name><affiliation wicri:level="3"><nlm:affiliation>Institute of Chemical Technology, Prague, Czech Republic.</nlm:affiliation><country xml:lang="fr">République tchèque</country><wicri:regionArea>Institute of Chemical Technology, Prague</wicri:regionArea><placeName><settlement type="city">Prague</settlement><region type="région" nuts="2">Bohême centrale</region></placeName></affiliation></author><author><name sortKey="Werner, L" sort="Werner, L" uniqKey="Werner L" first="L" last="Werner">L. Werner</name><affiliation wicri:level="3"><nlm:affiliation>Institute of Chemical Technology, Prague, Czech Republic.</nlm:affiliation><country xml:lang="fr">République tchèque</country><wicri:regionArea>Institute of Chemical Technology, Prague</wicri:regionArea><placeName><settlement type="city">Prague</settlement><region type="région" nuts="2">Bohême centrale</region></placeName></affiliation></author><author><name sortKey="Blanco Gonzalez, E" sort="Blanco Gonzalez, E" uniqKey="Blanco Gonzalez E" first="E" last="Blanco-González">E. Blanco-González</name><affiliation wicri:level="1"><nlm:affiliation>Department of Physical and Analytical Chemistry, Faculty of Chemistry, University of Oviedo, Oviedo, Spain.</nlm:affiliation><country xml:lang="fr">Espagne</country><wicri:regionArea>Department of Physical and Analytical Chemistry, Faculty of Chemistry, University of Oviedo, Oviedo</wicri:regionArea><wicri:noRegion>Oviedo</wicri:noRegion></affiliation></author><author><name sortKey="Montes Bay N, M" sort="Montes Bay N, M" uniqKey="Montes Bay N M" first="M" last="Montes-Bay N">M. Montes-Bay N</name><affiliation wicri:level="1"><nlm:affiliation>Department of Physical and Analytical Chemistry, Faculty of Chemistry, University of Oviedo, Oviedo, Spain.</nlm:affiliation><country xml:lang="fr">Espagne</country><wicri:regionArea>Department of Physical and Analytical Chemistry, Faculty of Chemistry, University of Oviedo, Oviedo</wicri:regionArea><wicri:noRegion>Oviedo</wicri:noRegion></affiliation></author><author><name sortKey="Joven, J" sort="Joven, J" uniqKey="Joven J" first="J" last="Joven">J. Joven</name><affiliation wicri:level="1"><nlm:affiliation>Unitat de Recerca Biomèdica, Hospital Universitari Sant Joan, Institut d'Investigació Sanitària Pere Virgili, Universitat Rovira i Virgili, Reus, Spain.</nlm:affiliation><country xml:lang="fr">Espagne</country><wicri:regionArea>Unitat de Recerca Biomèdica, Hospital Universitari Sant Joan, Institut d'Investigació Sanitària Pere Virgili, Universitat Rovira i Virgili, Reus</wicri:regionArea><wicri:noRegion>Reus</wicri:noRegion></affiliation></author><author><name sortKey="Viollet, B" sort="Viollet, B" uniqKey="Viollet B" first="B" last="Viollet">B. Viollet</name><affiliation wicri:level="3"><nlm:affiliation>INSERM U1016, Institut Cochin, Paris, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>INSERM U1016, Institut Cochin, Paris</wicri:regionArea><placeName><region type="region">Île-de-France</region><region type="old region">Île-de-France</region><settlement type="city">Paris</settlement></placeName></affiliation></author><author><name sortKey="Neuzil, J" sort="Neuzil, J" uniqKey="Neuzil J" first="J" last="Neuzil">J. Neuzil</name><affiliation wicri:level="3"><nlm:affiliation>Institute of Chemical Technology, Prague, Czech Republic.</nlm:affiliation><country xml:lang="fr">République tchèque</country><wicri:regionArea>Institute of Chemical Technology, Prague</wicri:regionArea><placeName><settlement type="city">Prague</settlement><region type="région" nuts="2">Bohême centrale</region></placeName></affiliation></author><author><name sortKey="Menendez, J A" sort="Menendez, J A" uniqKey="Menendez J" first="J A" last="Menendez">J A Menendez</name><affiliation wicri:level="1"><nlm:affiliation>ProCURE (Program Against Cancer Therapeutic Resistance), Metabolism & Cancer Group, Catalan Institute of Oncology, Girona, Catalonia, Spain.</nlm:affiliation><country xml:lang="fr">Espagne</country><wicri:regionArea>ProCURE (Program Against Cancer Therapeutic Resistance), Metabolism & Cancer Group, Catalan Institute of Oncology, Girona, Catalonia</wicri:regionArea><wicri:noRegion>Catalonia</wicri:noRegion></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PubMed</idno><date when="2017">2017</date><idno type="RBID">pubmed:29059169</idno><idno type="pmid">29059169</idno><idno type="doi">10.1038/onc.2017.367</idno><idno type="wicri:Area/PubMed/Corpus">000245</idno><idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Corpus" wicri:corpus="PubMed">000245</idno><idno type="wicri:Area/PubMed/Curation">000244</idno><idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Curation">000244</idno><idno type="wicri:Area/PubMed/Checkpoint">000244</idno><idno type="wicri:explorRef" wicri:stream="Checkpoint" wicri:step="PubMed">000244</idno><idno type="wicri:Area/Ncbi/Merge">005083</idno><idno type="wicri:Area/Ncbi/Curation">005083</idno><idno type="wicri:Area/Ncbi/Checkpoint">005083</idno><idno type="wicri:Area/Main/Merge">000801</idno><idno type="wicri:Area/Main/Curation">000806</idno><idno type="wicri:Area/Main/Exploration">000806</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en">Metformin regulates global DNA methylation via mitochondrial one-carbon metabolism.</title><author><name sortKey="Cuyas, E" sort="Cuyas, E" uniqKey="Cuyas E" first="E" last="Cuyàs">E. Cuyàs</name><affiliation wicri:level="1"><nlm:affiliation>ProCURE (Program Against Cancer Therapeutic Resistance), Metabolism & Cancer Group, Catalan Institute of Oncology, Girona, Catalonia, Spain.</nlm:affiliation><country xml:lang="fr">Espagne</country><wicri:regionArea>ProCURE (Program Against Cancer Therapeutic Resistance), Metabolism & Cancer Group, Catalan Institute of Oncology, Girona, Catalonia</wicri:regionArea><wicri:noRegion>Catalonia</wicri:noRegion></affiliation></author><author><name sortKey="Fernandez Arroyo, S" sort="Fernandez Arroyo, S" uniqKey="Fernandez Arroyo S" first="S" last="Fernández-Arroyo">S. Fernández-Arroyo</name><affiliation wicri:level="1"><nlm:affiliation>Unitat de Recerca Biomèdica, Hospital Universitari Sant Joan, Institut d'Investigació Sanitària Pere Virgili, Universitat Rovira i Virgili, Reus, Spain.</nlm:affiliation><country xml:lang="fr">Espagne</country><wicri:regionArea>Unitat de Recerca Biomèdica, Hospital Universitari Sant Joan, Institut d'Investigació Sanitària Pere Virgili, Universitat Rovira i Virgili, Reus</wicri:regionArea><wicri:noRegion>Reus</wicri:noRegion></affiliation></author><author><name sortKey="Verdura, S" sort="Verdura, S" uniqKey="Verdura S" first="S" last="Verdura">S. Verdura</name><affiliation wicri:level="1"><nlm:affiliation>ProCURE (Program Against Cancer Therapeutic Resistance), Metabolism & Cancer Group, Catalan Institute of Oncology, Girona, Catalonia, Spain.</nlm:affiliation><country xml:lang="fr">Espagne</country><wicri:regionArea>ProCURE (Program Against Cancer Therapeutic Resistance), Metabolism & Cancer Group, Catalan Institute of Oncology, Girona, Catalonia</wicri:regionArea><wicri:noRegion>Catalonia</wicri:noRegion></affiliation></author><author><name sortKey="Garcia, R F" sort="Garcia, R F" uniqKey="Garcia R" first="R F" last="García">R F García</name><affiliation wicri:level="1"><nlm:affiliation>Department of Physical and Analytical Chemistry, Faculty of Chemistry, University of Oviedo, Oviedo, Spain.</nlm:affiliation><country xml:lang="fr">Espagne</country><wicri:regionArea>Department of Physical and Analytical Chemistry, Faculty of Chemistry, University of Oviedo, Oviedo</wicri:regionArea><wicri:noRegion>Oviedo</wicri:noRegion></affiliation></author><author><name sortKey="Stursa, J" sort="Stursa, J" uniqKey="Stursa J" first="J" last="Stursa">J. Stursa</name><affiliation wicri:level="3"><nlm:affiliation>Institute of Chemical Technology, Prague, Czech Republic.</nlm:affiliation><country xml:lang="fr">République tchèque</country><wicri:regionArea>Institute of Chemical Technology, Prague</wicri:regionArea><placeName><settlement type="city">Prague</settlement><region type="région" nuts="2">Bohême centrale</region></placeName></affiliation></author><author><name sortKey="Werner, L" sort="Werner, L" uniqKey="Werner L" first="L" last="Werner">L. Werner</name><affiliation wicri:level="3"><nlm:affiliation>Institute of Chemical Technology, Prague, Czech Republic.</nlm:affiliation><country xml:lang="fr">République tchèque</country><wicri:regionArea>Institute of Chemical Technology, Prague</wicri:regionArea><placeName><settlement type="city">Prague</settlement><region type="région" nuts="2">Bohême centrale</region></placeName></affiliation></author><author><name sortKey="Blanco Gonzalez, E" sort="Blanco Gonzalez, E" uniqKey="Blanco Gonzalez E" first="E" last="Blanco-González">E. Blanco-González</name><affiliation wicri:level="1"><nlm:affiliation>Department of Physical and Analytical Chemistry, Faculty of Chemistry, University of Oviedo, Oviedo, Spain.</nlm:affiliation><country xml:lang="fr">Espagne</country><wicri:regionArea>Department of Physical and Analytical Chemistry, Faculty of Chemistry, University of Oviedo, Oviedo</wicri:regionArea><wicri:noRegion>Oviedo</wicri:noRegion></affiliation></author><author><name sortKey="Montes Bay N, M" sort="Montes Bay N, M" uniqKey="Montes Bay N M" first="M" last="Montes-Bay N">M. Montes-Bay N</name><affiliation wicri:level="1"><nlm:affiliation>Department of Physical and Analytical Chemistry, Faculty of Chemistry, University of Oviedo, Oviedo, Spain.</nlm:affiliation><country xml:lang="fr">Espagne</country><wicri:regionArea>Department of Physical and Analytical Chemistry, Faculty of Chemistry, University of Oviedo, Oviedo</wicri:regionArea><wicri:noRegion>Oviedo</wicri:noRegion></affiliation></author><author><name sortKey="Joven, J" sort="Joven, J" uniqKey="Joven J" first="J" last="Joven">J. Joven</name><affiliation wicri:level="1"><nlm:affiliation>Unitat de Recerca Biomèdica, Hospital Universitari Sant Joan, Institut d'Investigació Sanitària Pere Virgili, Universitat Rovira i Virgili, Reus, Spain.</nlm:affiliation><country xml:lang="fr">Espagne</country><wicri:regionArea>Unitat de Recerca Biomèdica, Hospital Universitari Sant Joan, Institut d'Investigació Sanitària Pere Virgili, Universitat Rovira i Virgili, Reus</wicri:regionArea><wicri:noRegion>Reus</wicri:noRegion></affiliation></author><author><name sortKey="Viollet, B" sort="Viollet, B" uniqKey="Viollet B" first="B" last="Viollet">B. Viollet</name><affiliation wicri:level="3"><nlm:affiliation>INSERM U1016, Institut Cochin, Paris, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>INSERM U1016, Institut Cochin, Paris</wicri:regionArea><placeName><region type="region">Île-de-France</region><region type="old region">Île-de-France</region><settlement type="city">Paris</settlement></placeName></affiliation></author><author><name sortKey="Neuzil, J" sort="Neuzil, J" uniqKey="Neuzil J" first="J" last="Neuzil">J. Neuzil</name><affiliation wicri:level="3"><nlm:affiliation>Institute of Chemical Technology, Prague, Czech Republic.</nlm:affiliation><country xml:lang="fr">République tchèque</country><wicri:regionArea>Institute of Chemical Technology, Prague</wicri:regionArea><placeName><settlement type="city">Prague</settlement><region type="région" nuts="2">Bohême centrale</region></placeName></affiliation></author><author><name sortKey="Menendez, J A" sort="Menendez, J A" uniqKey="Menendez J" first="J A" last="Menendez">J A Menendez</name><affiliation wicri:level="1"><nlm:affiliation>ProCURE (Program Against Cancer Therapeutic Resistance), Metabolism & Cancer Group, Catalan Institute of Oncology, Girona, Catalonia, Spain.</nlm:affiliation><country xml:lang="fr">Espagne</country><wicri:regionArea>ProCURE (Program Against Cancer Therapeutic Resistance), Metabolism & Cancer Group, Catalan Institute of Oncology, Girona, Catalonia</wicri:regionArea><wicri:noRegion>Catalonia</wicri:noRegion></affiliation></author></analytic><series><title level="j">Oncogene</title><idno type="eISSN">1476-5594</idno><imprint><date when="2017" type="published">2017</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">The anti-diabetic biguanide metformin may exert health-promoting effects via metabolic regulation of the epigenome. Here we show that metformin promotes global DNA methylation in non-cancerous, cancer-prone and metastatic cancer cells by decreasing S-adenosylhomocysteine (SAH), a strong feedback inhibitor of S-adenosylmethionine (SAM)-dependent DNA methyltransferases, while promoting the accumulation of SAM, the universal methyl donor for cellular methylation. Using metformin and a mitochondria/complex I (mCI)-targeted analog of metformin (norMitoMet) in experimental pairs of wild-type and AMP-activated protein kinase (AMPK)-, serine hydroxymethyltransferase 2 (SHMT2)- and mCI-null cells, we provide evidence that metformin increases the SAM:SAH ratio-related methylation capacity by targeting the coupling between serine mitochondrial one-carbon flux and CI activity. By increasing the contribution of one-carbon units to the SAM from folate stores while decreasing SAH in response to AMPK-sensed energetic crisis, metformin can operate as a metabolo-epigenetic regulator capable of reprogramming one of the key conduits linking cellular metabolism to the DNA methylation machinery.Oncogene advance online publication, 23 October 2017; doi:10.1038/onc.2017.367.</div></front></TEI><affiliations><list><country><li>Espagne</li><li>France</li><li>République tchèque</li></country><region><li>Bohême centrale</li><li>Île-de-France</li></region><settlement><li>Paris</li><li>Prague</li></settlement></list><tree><country name="Espagne"><noRegion><name sortKey="Cuyas, E" sort="Cuyas, E" uniqKey="Cuyas E" first="E" last="Cuyàs">E. Cuyàs</name></noRegion><name sortKey="Blanco Gonzalez, E" sort="Blanco Gonzalez, E" uniqKey="Blanco Gonzalez E" first="E" last="Blanco-González">E. Blanco-González</name><name sortKey="Fernandez Arroyo, S" sort="Fernandez Arroyo, S" uniqKey="Fernandez Arroyo S" first="S" last="Fernández-Arroyo">S. Fernández-Arroyo</name><name sortKey="Garcia, R F" sort="Garcia, R F" uniqKey="Garcia R" first="R F" last="García">R F García</name><name sortKey="Joven, J" sort="Joven, J" uniqKey="Joven J" first="J" last="Joven">J. Joven</name><name sortKey="Menendez, J A" sort="Menendez, J A" uniqKey="Menendez J" first="J A" last="Menendez">J A Menendez</name><name sortKey="Montes Bay N, M" sort="Montes Bay N, M" uniqKey="Montes Bay N M" first="M" last="Montes-Bay N">M. Montes-Bay N</name><name sortKey="Verdura, S" sort="Verdura, S" uniqKey="Verdura S" first="S" last="Verdura">S. Verdura</name></country><country name="République tchèque"><region name="Bohême centrale"><name sortKey="Stursa, J" sort="Stursa, J" uniqKey="Stursa J" first="J" last="Stursa">J. Stursa</name></region><name sortKey="Neuzil, J" sort="Neuzil, J" uniqKey="Neuzil J" first="J" last="Neuzil">J. Neuzil</name><name sortKey="Werner, L" sort="Werner, L" uniqKey="Werner L" first="L" last="Werner">L. Werner</name></country><country name="France"><region name="Île-de-France"><name sortKey="Viollet, B" sort="Viollet, B" uniqKey="Viollet B" first="B" last="Viollet">B. Viollet</name></region></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
EXPLOR_STEP=$WICRI_ROOT/Wicri/Asie/explor/AustralieFrV1/Data/Main/Exploration
HfdSelect -h $EXPLOR_STEP/biblio.hfd -nk 000806 | SxmlIndent | more
Ou
HfdSelect -h $EXPLOR_AREA/Data/Main/Exploration/biblio.hfd -nk 000806 | SxmlIndent | more
Pour mettre un lien sur cette page dans le réseau Wicri
{{Explor lien
|wiki= Wicri/Asie
|area= AustralieFrV1
|flux= Main
|étape= Exploration
|type= RBID
|clé= pubmed:29059169
|texte= Metformin regulates global DNA methylation via mitochondrial one-carbon metabolism.
}}
Pour générer des pages wiki
HfdIndexSelect -h $EXPLOR_AREA/Data/Main/Exploration/RBID.i -Sk "pubmed:29059169" \
| HfdSelect -Kh $EXPLOR_AREA/Data/Main/Exploration/biblio.hfd \
| NlmPubMed2Wicri -a AustralieFrV1
| This area was generated with Dilib version V0.6.33. |  |