PXD018251

PXD018251 is an original dataset announced via ProteomeXchange.

Title	Formaldehyde regulates one-carbon metabolism through S-adenosylmethionine biosynthesis
Description	One-carbon metabolism is a universal hub for cellular metabolism and epigenetic regulation.1–3 Here, we report that formaldehyde (FA), a one-carbon unit that organisms produce in substantial quantities through folate metabolism,4 is a regulator of the one-carbon cycle via the biosynthesis of S-adenosyl-L-methionine (SAM), an essential one-carbon building block for synthesis of nucleotides, amino acids, and methylated nucleic acids and proteins.5 Activity-based protein profiling (ABPP) in mouse liver tissue identifies FA-sensitive cysteine sites across the proteome, revealing several one-carbon cycle targets including S-adenosylmethionine synthetase isoform 1 (MAT1A), the terminal enzyme in SAM biosynthesis. Biochemical studies of the formaldehyde-MAT1A interaction establish FA-dependent inhibition of MAT1A activity through a conserved C120 site, as the MAT2A isoform lacking this cysteine is not FA-sensitive. CRISPR knockout-generated HepG2 cell models that predominantly express either MAT1A or MAT2A show that MAT1A-positive cells respond to FA treatment in a dose-dependent manner by decreasing their SAM levels and downstream RNA methylation, whereas the MAT2A-positive cells are not affected by FA. Our findings reveal an unexpected interplay between SAM and FA, two central one-carbon units to influence the overall methylation potential of the cell.
HostingRepository	PRIDE
AnnounceDate	2023-11-14
AnnouncementXML	Submission_2023-11-14_09:11:33.806.xml
DigitalObjectIdentifier	https://dx.doi.org/10.6019/PXD018251
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Supported dataset by repository
PrimarySubmitter	Kevin Bruemmer
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2020-03-30 00:26:09	ID requested
1	2023-11-02 17:08:08	announced
⏵ 2	2023-11-14 09:11:34	announced	2023-11-14: Updated project metadata.

10.6019/PXD018251;

submitter keyword: cysteine, formaldehyde,Mouse, one-carbon metabolism, Liver, LC-MS/MS

Christopher J. Chang
contact affiliation	University of California, Berkeley Dept. of Chemistry Dept. of Molecular and Cell Biology Member, Helen Wills Neuroscience Institue
contact email	chrischang@berkeley.edu
lab head
Kevin Bruemmer
contact affiliation	University of California, Berkeley
contact email	kbruem@berkeley.edu
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD018251
     1. Label: PRIDE project
     2. Name: Formaldehyde regulates one-carbon metabolism through S-adenosylmethionine biosynthesis