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Salmonella: Killing Macrophages via Glycolysis Enzymes

Caspases are aspartate-specific cysteine proteases that play critical roles in apoptosis and inflammation. Caspase-1 is essential during inflammation due to its role in the activation of cytokine signaling pathways. Despite this important role, few caspase-1 substrates have been identified to date, and those substrates do not account for the wide range of actions of the protease.

41 proteins are directly cleaved by caspase-1.

To better understand the function of caspase-1, Wei Shao and colleagues embarked on a systematic identification of its cellular substrates. Using the diagonal gel proteomic approach, they identified 41 proteins that are directly cleaved by caspase-1. Among these were chaperones, cytoskeletal and translation machinery proteins, as well as proteins involved in immunity. Surprisingly, several proteins involved in the glycolysis pathway were also identified as caspase-1 substrates. The researchers showed that Salmonella infection, which is associated with pyroptosis, a specialized form of cell death mediated by caspase-1, causes a pronounced degradation of these glycolysis enzymes and lowers the glycolytic rate of wild-type macrophages but not that of caspase-1-deficient cells. Since glycolysis is essential for macrophage survival and activation, the cleavage of the glycolysis enzymes likely represents an essential step in toxic cell death associated with Salmonella infection.

FOOTNOTES

See referenced article, J. Biol. Chem. 2007, 282, 36321-36329

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