Chemical Probe to Identify the Cellular Targets of the Reactive Lipid Metabolite 2-trans-Hexadecenal
Year: 2018
Type: article
Abstract: Lipid-derived electrophiles (LDEs) are reactive metabolites, which can covalently modify proteins and DNA and regulate diverse cellular processes. 2- trans-Hexadecenal (2-HD) is a byproduct of sphingolipid metabolism, involved in cytoskeletal reorganization, DNA damage, and apoptosis. In addition, the loss of ALDH3A2, an enzyme removing 2-HD in cells, is responsible for Sjörgen-Larsson Syndrome (SJS), suggesting that accumulation of 2-HD could lead to pathogenesis. However, the targets and the precise mechanisms of 2-HD are not well characterized. Herein, we report an alkyne-2-HD derivative as a bioorthogonal probe to explore the functions of 2-HD. We identified more than 500 potential cellular targets. Among them, the pro-apoptotic protein Bax can be covalently modified by 2-HD directly at the conserved Cys62 residue. Our work provided new chemical tools to explore the cellular functions of LDEs and revealed new mechanistic insights of the deregulation of lipid metabolism in diseases.
Source: ACS Chemical Biology
Authors: Gopala Krishna Jarugumilli, Jong-Ryoul Choi, PuiYee Chan, Meilan Yu, Yang Sun, Baoen Chen, Jixiao Niu, Michael DeRan, Baohui Zheng, Raphael Zoeller, Cheng Lin, Xu Wu
Language: English
Subfield: Organic Chemistry
Field: Chemistry
Domain: Physical Sciences
Open Access status: green
Awards: Metabolic regulation of cellular junction proteins, A high throughput screen for inhibitors of mammalian glycerolipid biosynthesis, Chemical approach to study autopalmitoylation of transcription factors, Metabolic regulation of YAP oncogenic function in tumorigenesis, Legacy Support During Closure of the Mass Spectrometry Resource for Biology and Medicine, Mass Spectrometry Resource for Biology and Medicine
OpenAlex ID: W2795868113