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Identification of Intracellular Signaling Events Induced in Viable Cells by Interaction with Neighboring Cells Undergoing Apoptotic Cell Death
09:18

Identification of Intracellular Signaling Events Induced in Viable Cells by Interaction with Neighboring Cells Undergoing Apoptotic Cell Death

Published on: December 27, 2016

Regulation of the apoptosis-necrosis switch

Pierluigi Nicotera1, Gerry Melino

  • 1Medical Research Council, Toxicology Unit, Leicester, UK. pn10@le.ac.uk

Oncogene
|April 13, 2004
PubMed

Insights

Cell death pathways are more diverse than previously thought. Apoptosis and necrosis can occur simultaneously, suggesting distinct cellular execution routes in vivo.

Area of Science:

  • Cellular Biology
  • Molecular Biology
  • Pathology

Background:

  • The execution of programmed cell death, or apoptosis, is generally understood to involve pathways converging on caspase proteases.
  • However, emerging evidence indicates that apoptosis-like features can manifest even with caspase inhibition.
  • Pathological conditions often exhibit intertwined apoptosis and non-apoptotic cell death, suggesting alternative in vivo execution pathways.

Purpose of the Study:

  • To explore the complexity of cellular death execution pathways beyond the canonical caspase-dependent apoptosis.
  • To investigate the interplay between apoptosis and necrosis under various conditions, particularly in vivo.
  • To identify molecular switches that differentiate between apoptotic and necrotic cell death.

Main Methods:

  • Review and synthesis of existing evidence on cellular death mechanisms.
  • Analysis of molecular events distinguishing apoptosis from necrosis.
  • Investigation of adenosine triphosphate-dependent steps and reactive oxygen/nitrogen species sensitivity in cell death regulation.

Main Results:

  • Cellular death is not exclusively mediated by caspase-dependent apoptosis.
  • Apoptotic and non-apoptotic (necrotic) cell death paradigms can occur concurrently, especially in pathological contexts.
  • Molecular switches, including ATP-dependent steps and reactive species, regulate the divergence between apoptosis and necrosis.

Conclusions:

  • Cells possess diverging execution pathways for cell death, not solely reliant on caspases.
  • The distinction between apoptosis and necrosis is regulated by specific molecular events.
  • Caspase activation itself can paradoxically lead to necrosis through mechanisms like ion overload.

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