Endogenously produced cyanide supports bioenergetics and exerts cytoprotective effects in mammals_Mice-liver

ABSTRACT: Small, gaseous molecules, known as gasotransmitters (NO, CO, H2S), are produced endogenously in mammalian cells and serve important biological roles. Cyanide (CN) is 35 known as an endogenous mediator in plants and bacteria, while in mammals it has been mainly viewed as a toxin. Here we show that low concentrations of CN are endogenously generated in mouse liver and human hepatocytes from glycine and HOCl-in lysosomes. CN diffuses out of the lysosome to reach various cellular compartments and is detectable in circulating blood. Endogenous CN–via protein cysteine cyanylation and removal of glutathione from proteins 40–exerts pluripotent effects on cell metabolism and gene expression. Endogenous CN production supports cellular ATP production, in part, via increased free fatty acid oxidation. CN also supports cell proliferation and exerts cytoprotective effects. Controlled CN donation exerts cytoprotective effects in vitro and in vivo models of hypoxia and reoxygenation. In this part of the study, we used liver samples from WT mice that were either treated with glycine or left untreated. Glycine is known to produce cyanide as a by-product of metabolism. Our objective was to identify the first the targets of cysteine cyanilation. As no enrichment method is available for this modification, we employed direct detection of cyanilated cysteines peptides in the proteome.

INSTRUMENT(S): timsTOF Pro 2

ORGANISM(S): Mus Musculus (mouse)

TISSUE(S): Liver

SUBMITTER: Jovan Petric  

LAB HEAD: Dr Milos

PROVIDER: PXD046065 | Pride | 2025-05-06

REPOSITORIES: Pride