A histone deacetylase 3 and mitochondrial complex I axis regulates toxic formaldehyde production

What are people’s thoughts on this… (@John_Hemming and others who are knowledgeable about this area)…

In Science this week:

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.


One person’s (Biochem professor) interpretation of this research:

SAMe is important to manage 1 carbon metabolism. Its level drops substantially after puberty and must be taken as a supplement to maintain health. Otherwise, formaldehyde becomes a toxic substance in your body, damaging histones and DNA methylation.


It looks like a non histone activity of HDAC 3.