Related Experiment Video

Updated: Sep 28, 2026

Lighting Up the Pathways to Caspase Activation Using Bimolecular Fluorescence Complementation
08:47

Lighting Up the Pathways to Caspase Activation Using Bimolecular Fluorescence Complementation

Published on: March 5, 2018

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

Insights

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).
  • 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.

More Related Videos

Visualization of Inflammatory Caspases Induced Proximity in Human Monocyte-Derived Macrophages08:41

Visualization of Inflammatory Caspases Induced Proximity in Human Monocyte-Derived Macrophages

Published on: April 6, 2022

Activation of Apoptosis by Cytoplasmic Microinjection of Cytochrome c07:42

Activation of Apoptosis by Cytoplasmic Microinjection of Cytochrome c

Published on: June 29, 2011

Related Concept Videos

Caspases01:24

Caspases

Caspase, a family of cysteine proteases, serve as effectors in apoptosis. The ced3 gene in C.elegans was first identified to be involved in apoptosis. This gene encodes the ced-3 caspase that is similar to the interleukin-1-beta converting enzyme or ICE in mammals. In addition to apoptosis, caspases also function in the inflammatory response. Inflammatory caspases are essential in activating pro-inflammatory cytokines that recruit immune cells and block the replication of pathogens inside cells.
The Intrinsic Apoptotic Pathway01:31

The Intrinsic Apoptotic Pathway

Internal cellular stress, such as cellular injury or hypoxia, triggers intrinsic apoptosis. The B-cell lymphoma 2 (Bcl-2) family of proteins are the primary regulators of the intrinsic apoptotic pathway. For example, during DNA damage, checkpoint proteins, such as Ataxia Telangiectasia Mutated (ATM protein) and Checkpoints Factor-2 (Chk2) proteins, are activated. These proteins phosphorylate p53 which further activates pro-apoptotic proteins, such as Bax, Bak, PUMA, and Noxa, and inhibits...
Apoptosis01:30

Apoptosis

Apoptosis is a combination of two Greek words, 'apo' and 'ptosis,' meaning separation and falling off, respectively. Hippocrates used this word to describe gangrene, which was caused due to bandaging of fractured bones. Apoptosis was distinguished from necrosis in 1970 when John Kerr reported observations of morphological changes occurring during apoptosis. During one experiment, he observed that the disruption of blood supply to the liver tissue resulted in a size reduction of the tissue.
The Extrinsic Apoptotic Pathway01:17

The Extrinsic Apoptotic Pathway

The extrinsic apoptotic pathway is initiated when extracellular death-inducing signals, such as specific cytokines, activate the death receptors expressed on the cell surface. The immune cells involved in this pathway are natural killer cells (NK cells) and cytotoxic T-lymphocytes. NK cells are critical in innate immune response, while cytotoxic T-lymphocytes are associated with adaptive immune response. These cells recognize specific receptors expressed on the altered cells and activate...
Phagocytosis of Apoptotic Cells01:17

Phagocytosis of Apoptotic Cells

Cells undergoing apoptosis form apoptotic bodies that must be removed immediately to prevent inflammation, autoimmune diseases, and necrosis. Phagocytosis is carried out by professional phagocytes such as macrophages or  immature dendritic cells. Non-professional phagocytes such as  epithelial cells and fibroblasts also take part in this process; however, they are not as effective as professional phagocytes. 
Normal cells contain receptors that prevent them from being recognized by phagocytes.
Autophagic Cell Death01:18

Autophagic Cell Death

Christian de Duve discovered “autophagy,” a process in which cellular components are engulfed by membrane-bound organelles called autophagosomes. The autophagosomes then fuse with lysosomes to digest the enclosed contents. Autophagy is generally activated in cells to prevent cell death. However, cell death is triggered when the damage is beyond repair.
Autophagy and Apoptosis
Autophagy can activate apoptosis. In normal conditions, the autophagy activating protein Beclin-1 and pro-apoptotic...