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Updated: Jun 24, 2026
07:17
Measuring Composition of CD95 Death-Inducing Signaling Complex and Processing of Procaspase-8 in this Complex
Published on: August 2, 2021
Lipid raft connection between extrinsic and intrinsic apoptotic pathways
Consuelo Gajate1, Fernando Gonzalez-Camacho, Faustino Mollinedo
1Centro de Investigación del Cáncer, Instituto de Biología Molecular y Celular del Cáncer, CSIC-Universidad de Salamanca, Campus Miguel de Unamuno, E-37007 Salamanca, Spain. cgajate@usal.es
Biochemical and Biophysical Research Communications
|April 3, 2009
Summary
The antitumor drug edelfosine triggers apoptosis in blood cancer cells by concentrating death signaling molecules within lipid rafts. These specialized raft structures, termed CASMERs, are crucial for initiating programmed cell death.
Area of Science:
- Cell Biology
- Molecular Oncology
- Biochemistry
Background:
- Apoptosis, or programmed cell death, is regulated by distinct extrinsic and intrinsic signaling pathways.
- The extrinsic pathway involves death receptors forming a death-inducing signaling complex (DISC).
- The intrinsic pathway is mediated by the mitochondrial-derived apoptosome.
Purpose of the Study:
- To investigate the role of lipid rafts in edelfosine-induced apoptosis in leukemic and multiple myeloma cells.
- To elucidate the mechanism by which edelfosine triggers apoptosis at the molecular and ultrastructural level.
Main Methods:
- Utilized ultrastructural approaches to observe cellular changes.
- Investigated the effect of edelfosine on lipid rafts, death receptors, DISC, and apoptosome components.
- Examined the impact of cholesterol depletion and replenishment on apoptotic signaling.
Main Results:
- Edelfosine induced aggregates of lipid rafts containing Fas/CD95 receptor and Fas-associated death domain (FADD) in leukemic cells.
- Death receptors, DISC, and apoptosome constituents, including caspases-8/-9/-10, were recruited into lipid rafts in multiple myeloma cells.
- Disruption of lipid rafts inhibited mitochondrial potential loss, caspase activation, and apoptosis; cholesterol replenishment restored these effects.
Conclusions:
- Lipid rafts serve as scaffolds concentrating extrinsic and intrinsic apoptotic signaling pathways.
- Clusters of apoptotic signaling molecule-enriched rafts (CASMERs) represent novel supramolecular entities crucial for apoptosis initiation.
- CASMERs play a significant role in edelfosine-induced apoptosis in hematological malignancies.
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