A chemical-genetic screen identifies ABHD12 as an oxidized-phosphatidylserine lipase.
Journal
Nature chemical biology
ISSN: 1552-4469
Titre abrégé: Nat Chem Biol
Pays: United States
ID NLM: 101231976
Informations de publication
Date de publication:
02 2019
02 2019
Historique:
received:
27
01
2018
accepted:
09
11
2018
pubmed:
16
1
2019
medline:
25
4
2019
entrez:
16
1
2019
Statut:
ppublish
Résumé
Reactive oxygen species (ROS) are transient, highly reactive intermediates or byproducts produced during oxygen metabolism. However, when innate mechanisms are unable to cope with sequestration of surplus ROS, oxidative stress results, in which excess ROS damage biomolecules. Oxidized phosphatidylserine (PS), a proapoptotic 'eat me' signal, is produced in response to elevated ROS, yet little is known regarding its chemical composition and metabolism. Here, we report a small molecule that generates ROS in different mammalian cells. We used this molecule to detect, characterize and study oxidized PS in mammalian cells. We developed a chemical-genetic screen to identify enzymes that regulate oxidized PS in mammalian cells and found that the lipase ABHD12 hydrolyzes oxidized PS. We validated these findings in different physiological settings including primary peritoneal macrophages and brains from Abhd12
Identifiants
pubmed: 30643283
doi: 10.1038/s41589-018-0195-0
pii: 10.1038/s41589-018-0195-0
pmc: PMC6420073
mid: EMS80470
doi:
Substances chimiques
Phosphatidylserines
0
Reactive Oxygen Species
0
Abhd12 protein, mouse
EC 3.1.1.23
Monoacylglycerol Lipases
EC 3.1.1.23
Lipase
EC 3.1.1.3
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
169-178Références
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