2. Academic Validation
  3. Chemical Probe to Identify the Cellular Targets of the Reactive Lipid Metabolite 2- trans-Hexadecenal

Chemical Probe to Identify the Cellular Targets of the Reactive Lipid Metabolite 2- trans-Hexadecenal

  • ACS Chem Biol. 2018 May 18;13(5):1130-1136. doi: 10.1021/acschembio.7b01063.
Gopala Krishna Jarugumilli 1,  Jong-Ryoul Choi 1,  PuiYee Chan 1,  Meilan Yu 2,  Yang Sun 1,  Baoen Chen 1,  Jixiao Niu 1,  Michael DeRan 1,  Baohui Zheng 1,  Raphael Zoeller 3,  Cheng Lin 2,  Xu Wu 1
Affiliations

Affiliations

  • 1 Cutaneous Biology Research Center , Massachusetts General Hospital, Harvard Medical School , Charlestown , Massachusetts 02129 , United States.
  • 2 Center for Biomedical Mass Spectrometry, Department of Biochemistry , Boston University School of Medicine , Boston , Massachusetts 02118-2526 , United States.
  • 3 Department of Physiology and Biophysics, Center for Advanced Biomedical Research , Boston University School of Medicine , Boston , Massachusetts 02118 , United States.
PMID: 29608264 DOI: 10.1021/acschembio.7b01063
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.

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