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Updated: Jul 5, 2026

Measuring Composition of CD95 Death-Inducing Signaling Complex and Processing of Procaspase-8 in this Complex
07:17

Measuring Composition of CD95 Death-Inducing Signaling Complex and Processing of Procaspase-8 in this Complex

Published on: August 2, 2021

Endosomal compartment contributes to the propagation of CD95/Fas-mediated signals in type II cells

Paola Matarrese1, Valeria Manganelli, Tina Garofalo

  • 1Department of Drug Research and Evaluation, Section of Cell Aging and Degeneration, Istituto Superiore di Sanità, viale Regina Elena 299, 00161 Rome, Italy.

The Biochemical Journal
|April 30, 2008
PubMed

Insights

Endocytosis is crucial for propagating CD95/Fas-activated cell death signaling in type II cells. Fas ligand triggers endocytosis, directing vesicles to mitochondria, which amplifies apoptosis.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Immunology

Background:

  • Intracellular signaling pathways regulate programmed cell death (apoptosis).
  • Diverse organelles participate in the signaling cascade following CD95/Fas receptor ligation.
  • Understanding the role of endocytosis in apoptosis is critical for cell death research.

Purpose of the Study:

  • To investigate the role of endocytosis in CD95/Fas-mediated apoptosis in type II cells.
  • To elucidate the mechanism by which endocytosis propagates cell death signaling.
  • To determine the relationship between endocytosis, organelle cross-talk, and apoptosis.

Main Methods:

  • Utilized CEM cells (type II cells) to study CD95/Fas signaling.
  • Investigated Fas ligand (FasL)-induced endocytosis and its dependence on caspase activation.
  • Tracked endocytic vesicle movement towards mitochondria.
  • Assessed mitochondrial membrane potential and apoptosis execution.
  • Compared signaling in drug-resistant CEM VBL100 cells.

Main Results:

  • CD95/Fas engagement triggers endocytosis independently of caspase activation.
  • FasL-induced endocytosis directs vesicles to the mitochondria, promoting organelle cross-talk.
  • This cross-talk leads to mitochondrial membrane potential loss and apoptosis.
  • Reduced endocytosis and organelle cross-talk correlated with reduced apoptosis in resistant cells.

Conclusions:

  • Endocytosis plays a key role in amplifying CD95/Fas-activated signaling in type II cells.
  • The movement of endocytic vesicles to mitochondria is essential for apoptosis execution.
  • Targeting endocytosis may offer therapeutic strategies for modulating apoptosis.

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