Formaldehyde regulates <i>S</i> -adenosylmethionine biosynthesis and one-carbon metabolism-Reference-Cited by-同舟云学术

Formaldehyde regulates S -adenosylmethionine biosynthesis and one-carbon metabolism

Published:2023-11-03 Issue:6670 Volume:382 Page:
ISSN:0036-8075
Container-title:Science
language:en
Short-container-title:Science

Author:

Pham Vanha N.¹^ORCID,Bruemmer Kevin J.¹^ORCID,Toh Joel D. W.¹,Ge Eva J.¹^ORCID,Tenney Logan¹^ORCID,Ward Carl C.²^ORCID,Dingler Felix A.³^ORCID,Millington Christopher L.³^ORCID,Garcia-Prieto Carlos A.⁴⁵^ORCID,Pulos-Holmes Mia C.²^ORCID,Ingolia Nicholas T.²^ORCID,Pontel Lucas B.⁴⁶^ORCID,Esteller Manel⁴⁷⁸⁹^ORCID,Patel Ketan J.³^ORCID,Nomura Daniel K.¹²¹⁰¹¹^ORCID,Chang Christopher J.¹²^ORCID

Affiliation:

1. Department of Chemistry, University of California, Berkeley, Berkeley, CA 94720, USA.

2. Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA 94720, USA.

3. MRC Weatherall Institute of Molecular Medicine, University of Oxford, John Radcliffe Hospital, Oxford, UK.

4. Josep Carreras Leukaemia Research Institute (IJC), Badalona, Barcelona, Catalonia, Spain.

5. Life Sciences Department, Barcelona Supercomputing Center (BSC), Barcelona, Spain.

6. Instituto de Investigación en Biomedicina de Buenos Aires (IBioBA), CONICET-Partner Institute of the Max Planck Society, Buenos Aires, Argentina.

7. Centro de Investigacion Biomedica en Red Cancer (CIBERONC), Calle Monforte de Lemos, Madrid, Spain.

8. Institucio Catalana de Recerca i Estudis Avançats (ICREA), Passeig de Lluis Companys, Barcelona, Spain.

9. Physiological Sciences Department, School of Medicine and Health Sciences, University of Barcelona, Feixa Llarga, l’Hospitalet de Llobregat, Spain.

10. Department of Nutritional Sciences and Toxicology, University of California, Berkeley, Berkeley, CA 94720, USA.

11. Innovative Genomics Institute, Berkeley, CA 94704, USA.

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.

Publisher

American Association for the Advancement of Science (AAAS)

Subject

Multidisciplinary

Link

https://www.science.org/doi/pdf/10.1126/science.abp9201

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