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The central executioners of apoptosis: caspases or mitochondria?
1Division of Cellular Immunology, La Jolla Institute for Allergy, San Diego, CA 92121, USA. dgreen5240@aol.com
Abstract:
Apoptosis is a type of cell death whose morphological appearance relies on the activation of caspase-family cysteine proteases. Recently, it has become clear that inhibition of caspases does not always prevent irreversible loss of cellular function, although it does prevent the acquisition of apoptotic morphology. Alterations in mitochondrial membrane structure and function can occur in a caspase-independent fashion and have a higher predictive value for cell death than caspase activation. Here, Douglas Green and Guido Kroemer argue that caspases might have a dual function in the apoptotic process: first, as signal-transduction molecules that act as facultative inducers of mitochondrial membrane changes, and, second, as processing enzymes that orchestrate the apoptotic phenotype. They propose a model for initiation of apoptosis in which mitochondria and caspases engage in a self-amplifying pathway of mutual activation.
Insights
Cell death, or apoptosis, involves caspases but can occur independently. Mitochondria and caspases may form a self-amplifying pathway, suggesting a dual role for caspases in cell death.
Area of Science:
- Cell Biology
- Biochemistry
Background:
- Apoptosis is characterized by specific morphological changes.
- Caspase activation is traditionally linked to apoptotic morphology.
Purpose of the Study:
- To explore the role of caspases in apoptosis beyond morphological changes.
- To investigate the involvement of mitochondria in caspase-independent cell death.
Main Methods:
- Review of existing literature on apoptosis and caspase function.
- Analysis of studies examining mitochondrial alterations in cell death.
Main Results:
- Caspase inhibition prevents apoptotic morphology but not all cell death.
- Mitochondrial membrane alterations can predict cell death independently of caspases.
- Caspases may act as inducers of mitochondrial changes and orchestrators of apoptotic phenotype.
Conclusions:
- Caspases might have a dual role in apoptosis: inducing mitochondrial changes and executing the apoptotic phenotype.
- A model of mutual activation between mitochondria and caspases is proposed for apoptosis initiation.