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Войти в исследования Science (New York, N.Y.) · 2023
Formaldehyde regulates S-adenosylmethionine biosynthesis and one-carbon metabolism.
СтатьяНазвание и аннотация: Перевод в очереди
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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
Аннотация
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.