AtSERPIN1 is an inhibitor of the metacaspase AtMC1-mediated cell death and autocatalytic processing in planta

New Phytol. 2018 May;218(3):1156-1166. doi: 10.1111/nph.14446. Epub 2017 Feb 3.


The hypersensitive response (HR) is a localized programmed cell death phenomenon that occurs in response to pathogen recognition at the site of attempted invasion. Despite more than a century of research on HR, little is known about how it is so tightly regulated and how it can be contained spatially to a few cells. AtMC1 is an Arabidopsis thaliana plant metacaspase that positively regulates the HR. Here, we used an unbiased approach to identify new AtMC1 regulators. Immunoaffinity purification of AtMC1-containing complexes led us to the identification of the protease inhibitor AtSerpin1. Our data clearly showed that coimmunoprecipitation between AtMC1 and AtSerpin1 and formation of a complex between them was lost upon mutation of the AtMC1 catalytic site, and that the AtMC1 prodomain was not required for the interaction. AtSerpin1 blocked AtMC1 self-processing and inhibited AtMC1-mediated cell death. Our results constitute an in vivo example of a Serpin acting as a suicide inhibitor in plants, reminiscent of the activity of animal or viral serpins on immune/cell death regulators, including caspase-1. These results indicate a conserved function of a protease inhibitor on cell death regulators from different kingdoms with unrelated modes of action (i.e. caspases vs metacaspases).

Keywords: hypersensitive response (HR); metacaspase; plant-pathogen interactions; programmed cell death; protease; serpin.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis*
  • Arabidopsis / cytology*
  • Arabidopsis / enzymology*
  • Arabidopsis Proteins / chemistry
  • Arabidopsis Proteins / metabolism*
  • Biocatalysis
  • Caspases / chemistry
  • Caspases / metabolism*
  • Immunoprecipitation
  • Proteasome Endopeptidase Complex / metabolism
  • Protein Binding
  • Protein Domains
  • Serpins / metabolism*


  • Arabidopsis Proteins
  • Serpin1 protein, Arabidopsis
  • Serpins
  • Caspases
  • MC1 protein, Arabidopsis
  • Proteasome Endopeptidase Complex