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Quantitative and Dynamic Catalogs of Proteins Released during Apoptotic and Necroptotic Cell Death

Maria C Tanzer1, Annika Frauenstein2, Che A Stafford3

  • 1Department of Proteomics and Signal Transduction, Max Planck Institute of Biochemistry, 82152 Martinsried, Germany.

Cell Reports
|January 30, 2020
PubMed

Insights

Tumor necrosis factor (TNF) triggers cell death pathways, apoptosis and necroptosis, releasing distinct proteins. Necroptosis releases lysosomal components, while apoptosis releases nucleosomes, impacting immune responses.

Area of Science:

  • Immunology
  • Cell Biology
  • Proteomics

Background:

  • Tumor necrosis factor (TNF) is a cytokine crucial for inflammation and cell death.
  • Apoptosis and necroptosis are distinct cell death pathways regulating immunogenicity through protein release.
  • Understanding protein release during these pathways is vital for comprehending immune responses.

Purpose of the Study:

  • To comprehensively analyze protein release during apoptosis and necroptosis using proteomics.
  • To gain a systems-level understanding of how different cell death pathways influence immunogenicity via secreted proteins.

Main Methods:

  • Mass spectrometry-based proteomics was employed to quantify protein release.
  • Time-course experiments were conducted on human myeloid cells undergoing apoptosis and necroptosis.

Main Results:

  • Hundreds of proteins were identified as released from human myeloid cells during both apoptosis and necroptosis.
  • Receptor shedding was observed in both cell death types.
  • Apoptotic cells uniquely released nucleosome components.
  • Necroptotic cells released lysosomal components via lysosomal exocytosis and showed reduced release of conventional cytokines.

Conclusions:

  • Apoptosis and necroptosis differentially regulate protein release, impacting immunogenicity.
  • Necroptosis involves early lysosomal exocytosis and distinct protein cargo compared to apoptosis.
  • These findings provide a detailed proteomic landscape of cell death-induced protein secretion.
Keywords:
TNFapoptosiscytokine releaseextracellular vesicleslysosomal exocytosismass spectrometrynecroptosisreceptor shedding

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