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Formaldehyde regulates S-adenosylmethionine biosynthesis and one-carbon metabolism.
Pham, Vanha N; Bruemmer, Kevin J; Toh, Joel D W; Ge, Eva J; Tenney, Logan; Ward, Carl C; Dingler, Felix A; Millington, Christopher L; Garcia-Prieto, Carlos A; Pulos-Holmes, Mia C; Ingolia, Nicholas T; Pontel, Lucas B; Esteller, Manel; Patel, Ketan J; Nomura, Daniel K; Chang, Christopher J.
Afiliação
  • Pham VN; Department of Chemistry, University of California, Berkeley, Berkeley, CA 94720, USA.
  • Bruemmer KJ; Department of Chemistry, University of California, Berkeley, Berkeley, CA 94720, USA.
  • Toh JDW; Department of Chemistry, University of California, Berkeley, Berkeley, CA 94720, USA.
  • Ge EJ; Department of Chemistry, University of California, Berkeley, Berkeley, CA 94720, USA.
  • Tenney L; Department of Chemistry, University of California, Berkeley, Berkeley, CA 94720, USA.
  • Ward CC; Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA 94720, USA.
  • Dingler FA; MRC Weatherall Institute of Molecular Medicine, University of Oxford, John Radcliffe Hospital, Oxford, UK.
  • Millington CL; MRC Weatherall Institute of Molecular Medicine, University of Oxford, John Radcliffe Hospital, Oxford, UK.
  • Garcia-Prieto CA; Josep Carreras Leukaemia Research Institute (IJC), Badalona, Barcelona, Catalonia, Spain.
  • Pulos-Holmes MC; Life Sciences Department, Barcelona Supercomputing Center (BSC), Barcelona, Spain.
  • Ingolia NT; Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA 94720, USA.
  • Pontel LB; Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA 94720, USA.
  • Esteller M; Josep Carreras Leukaemia Research Institute (IJC), Badalona, Barcelona, Catalonia, Spain.
  • Patel KJ; Instituto de Investigación en Biomedicina de Buenos Aires (IBioBA), CONICET-Partner Institute of the Max Planck Society, Buenos Aires, Argentina.
  • Nomura DK; Josep Carreras Leukaemia Research Institute (IJC), Badalona, Barcelona, Catalonia, Spain.
  • Chang CJ; Centro de Investigacion Biomedica en Red Cancer (CIBERONC), Calle Monforte de Lemos, Madrid, Spain.
Science ; 382(6670): eabp9201, 2023 11 03.
Article em En | MEDLINE | ID: mdl-37917677
ABSTRACT
One-carbon metabolism is an essential branch of cellular metabolism that intersects with epigenetic regulation. In this work, we show how formaldehyde (FA), a one-carbon unit derived from both endogenous sources and environmental exposure, regulates one-carbon metabolism by inhibiting the biosynthesis of S-adenosylmethionine (SAM), the major methyl donor in cells. FA reacts with privileged, hyperreactive cysteine sites in the proteome, including Cys120 in S-adenosylmethionine synthase isoform type-1 (MAT1A). FA exposure inhibited MAT1A activity and decreased SAM production with MAT-isoform specificity. A genetic mouse model of chronic FA overload showed a decrease n SAM and in methylation on selected histones and genes. Epigenetic and transcriptional regulation of Mat1a and related genes function as compensatory mechanisms for FA-dependent SAM depletion, revealing a biochemical feedback cycle between FA and SAM one-carbon units.
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: S-Adenosilmetionina / Carbono / Cisteína / Epigênese Genética / Formaldeído / Metionina Adenosiltransferase Idioma: En Ano de publicação: 2023 Tipo de documento: Article
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: S-Adenosilmetionina / Carbono / Cisteína / Epigênese Genética / Formaldeído / Metionina Adenosiltransferase Idioma: En Ano de publicação: 2023 Tipo de documento: Article