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[Apoptosis: molecular mechanisms]
1Unité INSERM 517 Mort cellulaire et cancer, Facultés de Médecine et de Pharmacie, Dijon. esolary@u-bourgogne.fr
Abstract:
Apoptosis is a genetically programmed cell death that is required for morphogenesis during embryogenic development and for tissue homeostasis in adult organisms. In most cases, apoptosis involves cytochrome c release from mitochondria. In the cytosol, cytochrome c combines with APAF-1 in the presence of ATP to activate caspase-9 that, in turn, activates effectors caspases such as caspase-3. Bcl-2 and related proteins control cytochrome c release from the mitochondria whereas IAP (for Inhibitor of APoptosis) molecules modulate the activity of caspases. Plasma membrane receptors such as Fas (CD95, APO-1), characterized by a so-called "death domain" in their cytoplasmic domain, can activate the caspase cascade through adaptator molecules such as FADD (Fas-Associated protein with a Death Domain). Dysregulation of the apoptotic machinery plays a role in the pathogenesis of various diseases and molecules involved in cell death pathways are potential therapeutic targets in immunologic, neurologic, cancer, infectious and inflammatory diseases.
Insights
Apoptosis, a programmed cell death, is vital for development and tissue health. Its pathways, involving mitochondria and caspases, are implicated in diseases, making them therapeutic targets.
Area of Science:
- Cell Biology
- Molecular Biology
- Biochemistry
Context:
- Apoptosis, or programmed cell death, is essential for embryonic development and maintaining tissue homeostasis in adults.
- The intrinsic pathway often involves the release of cytochrome c from mitochondria, initiating a caspase cascade.
- Extrinsic pathways can be triggered by plasma membrane receptors like Fas, also activating caspases.
Purpose:
- To outline the fundamental mechanisms of apoptosis.
- To describe the key molecular players and pathways involved in programmed cell death.
- To highlight the relevance of apoptosis in disease pathogenesis.
Summary:
- Apoptosis is a genetically programmed cell death crucial for development and homeostasis.
- Key events include mitochondrial cytochrome c release, caspase activation (caspase-9, caspase-3), and regulation by Bcl-2 and IAP proteins.
- Plasma membrane receptors like Fas, via FADD, can also initiate the caspase cascade.
Impact:
- Understanding apoptosis is critical for comprehending various diseases, including immunologic, neurologic, cancer, infectious, and inflammatory conditions.
- Molecules within cell death pathways represent promising therapeutic targets for a range of diseases.
- Dysregulation of apoptosis contributes to disease pathogenesis, underscoring its importance in medicine.