| First Author | Pham VN | Year | 2023 |
| Journal | Science | Volume | 382 |
| Issue | 6670 | Pages | eabp9201 |
| PubMed ID | 37917677 | Mgi Jnum | J:342485 |
| Mgi Id | MGI:7545598 | Doi | 10.1126/science.abp9201 |
| Citation | Pham VN, et al. (2023) Formaldehyde regulates S-adenosylmethionine biosynthesis and one-carbon metabolism. Science 382(6670):eabp9201 |
| abstractText | 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. |
