PXD046323

PXD046323 is an original dataset announced via ProteomeXchange.

Title	Endogenously produced cyanide supports bioenergetics and exerts cytoprotective effects in mammals_HepG2 cells treated with cyanide releasers
Description	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 HepG2 cells samples that were either treated with Amygdalin, Linamarin, Mandelonitrile, 1 uM KCN, 10 nM KCN or left untreated. Amygdalin, Linamarin and Mandelonitrile are known to release cyanide when broken down by metabolic processes. 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.
HostingRepository	PRIDE
AnnounceDate	2025-05-06
AnnouncementXML	Submission_2025-05-06_13:18:46.036.xml
DigitalObjectIdentifier	https://dx.doi.org/10.6019/PXD046323
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Supported dataset by repository
PrimarySubmitter	Jovan Petric
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	S-cyano-L-cysteine; acetylated residue; monohydroxylated residue; iodoacetamide derivatized residue
Instrument	timsTOF Pro 2

Revision	Datetime	Status	ChangeLog Entry
0	2023-10-23 07:18:29	ID requested
⏵ 1	2025-05-06 13:18:47	announced

10.1038/s42255-025-01225-w;

Zuhra K, Petrosino M, Janickova L, Petric J, Ascen, ç, ã, o K, Vignane T, Khalaf M, Philipp TM, Ravani S, Anand A, Martins V, Santos S, Erdemir S, Malkondu S, Sitek B, Kelestemur T, Kieronska-Rudek A, Majtan T, Filgueira L, Maric D, Chlopicki S, Hoogewijs D, Hask, ó G, Papapetropoulos A, Logue BA, Boss GR, Filipovic MR, Szabo C, Regulation of mammalian cellular metabolism by endogenous cyanide production. Nat Metab, 7(3):531-555(2025) [pubmed]

10.6019/PXD046323;

submitter keyword: Cyanilation, Cysteine modification

Dr Milos
contact affiliation	Leibniz-Institut für Analytische Wissenschaften - ISAS - e.V
contact email	milos.filipovic@isas.de
lab head
Jovan Petric
contact affiliation	Leibniz Institute for Analytical Sciences – ISAS – eV
contact email	jovan.petric@isas.de
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD046323
     1. Label: PRIDE project
     2. Name: Endogenously produced cyanide supports bioenergetics and exerts cytoprotective effects in mammals_HepG2 cells treated with cyanide releasers