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Related Experiment Videos

Apoptosomes: engines for caspase activation.

Jerry M Adams1, Suzanne Cory

  • 1The Walter and Eliza Hall Institute of Medical Research, Melbourne, 3050, Victoria, Australia. adams@wehi.edu.au

Current Opinion in Cell Biology
|December 11, 2002
PubMed
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Apoptosis initiation involves scaffold proteins like CED-4, Apaf-1, and Dark, which form apoptosomes. Their regulation and roles vary across species, with Apaf-1 amplifying mammalian caspase cascades.

Area of Science:

  • Cellular biology
  • Molecular biology
  • Biochemistry

Background:

  • Apoptosis, or programmed cell death, is crucial for development and tissue homeostasis.
  • Caspase activation, the central executioners of apoptosis, typically requires scaffold proteins to form apoptosomes.
  • Key scaffolds include CED-4 (C. elegans), Apaf-1 (mammals), and Dark (Drosophila).

Purpose of the Study:

  • To compare the regulation and biological roles of caspase scaffold proteins across different species.
  • To elucidate the mechanisms of apoptosome formation and activation.
  • To understand the initiation versus amplification roles of these scaffolds in apoptosis.

Main Methods:

  • Comparative analysis of scaffold protein structures and functions.
  • Investigation of regulatory interactions (e.g., CED-9 inhibition of CED-4).

Related Experiment Videos

  • Examination of activation pathways involving cytochrome c and mitochondrial damage.

    • Main Results:

    • Scaffold proteins oligomerize procaspases into apoptosomes, but their regulation differs significantly.
    • CED-4 is regulated by CED-9; Apaf-1 is inhibited by its WD40 region and activated by cytochrome c.
    • Dark's activation pathway appears independent of cytochrome c.
    • The Apaf-1/caspase-9 complex in mammals likely amplifies, rather than initiates, apoptosis.

    Conclusions:

    • Species-specific mechanisms govern scaffold protein function in apoptosis.
    • Cytochrome c is a key activator for mammalian Apaf-1 but not Drosophila Dark.
    • Mammalian apoptosis initiation may involve pathways distinct from the Apaf-1/caspase-9 amplification system.