Apoptosis commitment--translating survival signals into decisions on mitochondria
James A Keeble1, Andrew P Gilmore
1Wellcome Trust Centre for Cell-Matrix Research, Faculty of Life Sciences, University of Manchester, A.3034 Michael Smith Building, Oxford Road, Manchester M13 9PT, UK.
Abstract:
Most defective and unwanted cells die by apoptosis, an exquisitely controlled genetic programme for removing such cells without damaging the surrounding tissue. Once a cell has committed to apoptosis, the process is remarkably efficient, and is completed within a few minutes of initiation. This point of no return for an apoptotic cell is commonly held to be the point at which the outer mitochondrial membrane is permeabilised, a process regulated by the Bcl-2 family of proteins. How these proteins regulate this decision point is central to diseases such as cancer where apoptotic control is lost. In this review, we will discuss apoptotic signalling and how a cell makes the irreversible decision to die. We will focus on one set of survival signals, those derived by cell adhesion to the extracellular matrix (ECM), and use these to highlight the complexities of apoptotic signalling. In particular, we will illustrate how multiple signalling pathways converge to determine critical cell fate decisions.
Insights
Cells decide to undergo programmed cell death (apoptosis) through regulated mitochondrial outer membrane permeabilization. This review explores how survival signals, like extracellular matrix (ECM) adhesion, influence this critical cell fate decision.
Area of Science:
- Cell Biology
- Molecular Biology
- Biochemistry
Background:
- Apoptosis is a genetically controlled process for removing defective cells.
- The Bcl-2 protein family regulates the commitment to apoptosis.
- Dysregulation of apoptosis is implicated in diseases like cancer.
Purpose of the Study:
- To review apoptotic signaling pathways.
- To explain the irreversible decision-making process in apoptosis.
- To highlight the role of extracellular matrix (ECM) adhesion in cell survival signals.
Main Methods:
- Literature review of apoptotic signaling.
- Analysis of Bcl-2 protein family function.
- Discussion of cell adhesion signaling pathways.
Main Results:
- Apoptosis commitment is linked to mitochondrial outer membrane permeabilization.
- Multiple signaling pathways converge to determine cell fate.
- Extracellular matrix (ECM) adhesion provides survival signals that modulate apoptosis.
Conclusions:
- Understanding apoptotic signaling is crucial for disease research, particularly cancer.
- Cell fate decisions involve complex integration of various signaling inputs.
- The Bcl-2 family plays a key role in the decision to initiate apoptosis.
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