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Return of the Ice Age: Caspases Safeguard against Inflammatory Cell Death

Marcin Poreba1, Guy Salvesen1

  • 1Sanford Burnham Prebys Medical Discovery Institute, 10901 North Torrey Pines Road, La Jolla, CA 92037, USA.

Cell Chemical Biology
|May 20, 2017
PubMed

Insights

Researchers found a two-way link between apoptosis and pyroptosis, distinct cell death types. Differential gasdermin D cleavage determines the inflammatory outcome, with caspases playing opposing roles.

Area of Science:

  • Molecular Biology
  • Cell Biology
  • Immunology

Background:

  • Apoptosis and pyroptosis are distinct forms of regulated cell death.
  • These processes have opposing inflammatory outcomes.
  • Gasdermin D is a key executioner substrate in pyroptosis.

Purpose of the Study:

  • To elucidate the interplay between apoptosis and pyroptosis pathways.
  • To understand the role of gasdermin D cleavage in determining cell death outcomes.

Main Methods:

  • The study investigated the molecular mechanisms governing apoptosis and pyroptosis.
  • Differential caspase activity on gasdermin D was analyzed.

Main Results:

  • A bidirectional interplay between apoptosis and pyroptosis pathways was revealed.
  • Inflammatory caspases activate gasdermin D cleavage, promoting pyroptosis.
  • Apoptotic caspases inhibit gasdermin D cleavage, preventing pyroptosis.

Conclusions:

  • The balance of caspase activity dictates the inflammatory fate of the cell.
  • Differential gasdermin D cleavage is a critical checkpoint for regulated cell death outcomes.

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