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Cell-death networks

Hamid Kashkar1, Manolis Pasparakis2

  • 1University of Cologne, Faculty of Medicine and University Hospital of Cologne, Institute for Molecular Immunology, Cologne, Germany; University of Cologne, Center for Molecular Medicine Cologne (CMMC), Cologne, Germany; University of Cologne, Cologne Excellence Cluster for Aging and Aging-Associated Diseases (CECAD), Cologne, Germany.

Molecular Cell
|October 17, 2025
PubMed

Insights

Cell death pathways are interconnected, not rigidly defined. The availability of key molecules, not just initial signals, determines the cell death outcome, impacting disease therapies.

Area of Science:

  • Cellular biology
  • Molecular mechanisms of cell death

Background:

  • Cell death occurs via genetically regulated pathways with distinct tissue outcomes.
  • Traditional classification of cell death is rigid.

Purpose of the Study:

  • To explore the interconnectedness of cell death pathways.
  • To understand how molecular availability influences cell death modes.
  • To highlight implications for therapeutic targeting in diseases.

Main Methods:

  • Review of emerging evidence on cell death pathways.
  • Analysis of molecular interconnections between pathways.
  • Investigation of terminal executioners and substrates in cell death.

Main Results:

  • Cell death pathways are molecularly interconnected.
  • The mode of cell death depends on both apical signals and terminal executioner/substrate availability.
  • Traditional classifications are challenged by this interconnectedness.

Conclusions:

  • Cell death is a more dynamic and interconnected process than previously thought.
  • Understanding these connections is crucial for developing effective disease therapies.
  • Therapeutic strategies targeting cell death need to consider molecular availability.

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