A chemical-genetic screen identifies ABHD12 as an oxidized-phosphatidylserine lipase.

Reactive oxygen species are transient, highly reactive intermediates or byproducts produced during oxygen metabolism. However, when innate mechanisms are unable to cope with sequestration of surplus oxidative stress results, in which excess damage biomolecules. Oxidized phosphatidylserine (PS), a proapoptotic 'eat me' signal, is produced in response to elevated duanyu1670, yet little is known regarding its chemical composition and metabolism. Here, we report a small molecule that generates duanyu1670 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^-/- mice under inflammatory stress, and in the process, we functionally annotated an enzyme regulating oxidized PS in vivo.

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