A histone deacetylase 3 and mitochondrial complex I axis regulates toxic formaldehyde production.
Journal
Science advances
ISSN: 2375-2548
Titre abrégé: Sci Adv
Pays: United States
ID NLM: 101653440
Informations de publication
Date de publication:
19 05 2023
19 05 2023
Historique:
medline:
19
5
2023
pubmed:
17
5
2023
entrez:
17
5
2023
Statut:
ppublish
Résumé
Cells produce considerable genotoxic formaldehyde from an unknown source. We carry out a genome-wide CRISPR-Cas9 genetic screen in metabolically engineered HAP1 cells that are auxotrophic for formaldehyde to find this cellular source. We identify histone deacetylase 3 (HDAC3) as a regulator of cellular formaldehyde production. HDAC3 regulation requires deacetylase activity, and a secondary genetic screen identifies several components of mitochondrial complex I as mediators of this regulation. Metabolic profiling indicates that this unexpected mitochondrial requirement for formaldehyde detoxification is separate from energy generation. HDAC3 and complex I therefore control the abundance of a ubiquitous genotoxic metabolite.
Identifiants
pubmed: 37196082
doi: 10.1126/sciadv.adg2235
pmc: PMC10191432
doi:
Substances chimiques
histone deacetylase 3
EC 3.5.1.98
Histone Deacetylases
EC 3.5.1.98
Electron Transport Complex I
EC 7.1.1.2
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
eadg2235Subventions
Organisme : Wellcome Trust
Pays : United Kingdom
Organisme : Cancer Research UK
ID : 24455
Pays : United Kingdom
Organisme : Medical Research Council
ID : MR/T032413/1
Pays : United Kingdom
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