The caspase-1 digestome identifies the glycolysis pathway as a target during infection and septic shock

J Biol Chem. 2007 Dec 14;282(50):36321-9. doi: 10.1074/jbc.M708182200. Epub 2007 Oct 24.


Caspase-1 is an essential effector of inflammation, pyroptosis, and septic shock. Few caspase-1 substrates have been identified to date, and these substrates do not account for its wide range of actions. To understand the function of caspase-1, we initiated the systematic identification of its cellular substrates. Using the diagonal gel proteomic approach, we identified 41 proteins that are directly cleaved by caspase-1. Among these were chaperones, cytoskeletal and translation machinery proteins, and proteins involved in immunity. A series of unexpected proteins along the glycolysis pathway were also identified, including aldolase, triose-phosphate isomerase, glyceraldehyde-3-phosphate dehydrogenase, alpha-enolase, and pyruvate kinase. With the exception of the latter, the identified glycolysis enzymes were specifically cleaved in vitro by recombinant caspase-1, but not caspase-3. The enzymatic activity of wild-type glyceraldehyde-3-phosphate dehydrogenase, but not a non-cleavable mutant, was dampened by caspase-1 processing. In vivo, stimuli that fully activated caspase-1, including Salmonella typhimurium infection and septic shock, caused a pronounced processing of these proteins in the macrophage and diaphragm muscle, respectively. Notably, these stimuli inhibited glycolysis in wild-type cells compared with caspase-1-deficient cells. The systematic characterization of caspase-1 substrates identifies the glycolysis pathway as a caspase-1 target and provides new insights into its function during pyroptosis and septic shock.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Caspase 1 / genetics
  • Caspase 1 / metabolism*
  • Cell Line
  • Diaphragm / enzymology
  • Diaphragm / pathology
  • Glycolysis*
  • Humans
  • Macrophages, Peritoneal / enzymology*
  • Macrophages, Peritoneal / pathology
  • Mice
  • Mice, Knockout
  • Mutation
  • Proteome / genetics
  • Proteome / metabolism
  • Salmonella Infections / enzymology*
  • Salmonella Infections / genetics
  • Salmonella Infections / pathology
  • Salmonella typhimurium*
  • Shock, Septic / enzymology*
  • Shock, Septic / genetics
  • Shock, Septic / pathology
  • Substrate Specificity / genetics


  • Proteome
  • Caspase 1