Related Experiment Video
Updated: Jun 16, 2026
12:44
Use of LysoTracker to Detect Programmed Cell Death in Embryos and Differentiating Embryonic Stem Cells
Published on: October 11, 2012
A systems level strategy for analyzing the cell death network: implication in exploring the apoptosis/autophagy
1Department of Molecular Genetics, Weizmann Institute of Science, Rehovot 76100, Israel.
Cell Death and Differentiation
|February 13, 2010
Summary
This study reveals new connections between apoptosis and autophagy in mammalian cell death. Inhibiting caspase3 triggers autophagic cell death, highlighting the intricate network regulating cell fate.
Area of Science:
- Cellular Biology
- Molecular Biology
- Genetics
Background:
- Mammalian cell death involves apoptosis, autophagy, and programmed necrosis.
- Understanding intermodular connectivity in cell death pathways is limited.
- Systems-level approaches are needed to map these connections.
Purpose of the Study:
- To develop and apply a platform for assessing intermodular connectivity in cell death.
- To investigate the impact of gene perturbations on cell death performance.
- To identify genetic links between apoptosis and autophagy.
Main Methods:
- RNAi-mediated gene perturbations (single and double sets) targeting apoptotic and autophagic genes.
- Quantitative reporter assays for overall cell death responses.
- Molecular analysis of responses within functional modules.
- Epistatic analyses to determine genetic links between proteins.
- Computational analysis of protein-protein interaction databases.
Main Results:
- A novel platform identified connectivity between apoptosis and autophagy.
- Knockdown of caspase3 induced autophagic cell death, dependent on Atg5 or Beclin-1.
- A reciprocal connection between autophagic genes (Atg5, Beclin-1) and apoptosis was observed.
- A novel biochemical pathway linking Atg5 and caspase3 was computationally suggested.
Conclusions:
- The developed platform effectively maps cell death network connectivity.
- Casapse3 plays a critical role in switching cell death pathways.
- The findings provide a basis for future modeling of the complex cell death network.
More Related Videos
Related Concept Videos
01:18Autophagic 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...
Autophagy and Apoptosis
Autophagy can activate apoptosis. In normal conditions, the autophagy activating protein Beclin-1 and pro-apoptotic...
01:22Cellular Injury V: Apoptosis and Autophagy
Cells respond to damage and stress through highly coordinated processes that decide whether they survive or undergo controlled self-destruction. Two major pathways involved in this regulation are apoptosis, a type of programmed cell death, and autophagy, a survival mechanism that helps cells adapt to adverse conditions.ApoptosisApoptosis removes aged or injured cells to maintain tissue balance. During this process, the cell shrinks, chromatin condenses and fragments, and membrane-bound...
01:30Overview of Cell Death
Cell death is an essential process where the body gets rid of old or damaged cells. Cell proliferation and death need to be balanced, as an imbalance between the two may lead to cancer or autoimmune diseases.
Cell death was observed in the early 19th century, but there was no experimental evidence to prove it. In 1842, Carl Vogt first discovered cell death in a metamorphic toad; however, it was not termed ‘cell death.’ Scientists discovered different cell death pathways only in the 20th century...
Cell death was observed in the early 19th century, but there was no experimental evidence to prove it. In 1842, Carl Vogt first discovered cell death in a metamorphic toad; however, it was not termed ‘cell death.’ Scientists discovered different cell death pathways only in the 20th century...
01:30Apoptosis
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.
01:17The 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...
01:31The 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...