The regulation of the apoptotic pore-An immunological tightrope walk
Andreas Jenner1, Ana J Garcia-Saez1
1Institute for Genetics and Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), University of Cologne, Cologne, Germany.
Abstract:
Apoptotic pore formation in mitochondria is the pivotal point for cell death during mitochondrial apoptosis. It is regulated by BCL-2 family proteins in response to various cellular stress triggers and mediates mitochondrial outer membrane permeabilization (MOMP). This allows the release of mitochondrial contents into the cytosol, which triggers rapid cell death and clearance through the activation of caspases. However, under conditions of low caspase activity, the mitochondrial contents released into the cytosol through apoptotic pores serve as inflammatory signals and activate various inflammatory responses. In this chapter, we discuss how the formation of the apoptotic pore is regulated by BCL-2 proteins as well as other cellular or mitochondrial proteins and membrane lipids. Moreover, we highlight the importance of sublethal MOMP in the regulation of mitochondrial-activated inflammation and discuss its physiological consequences in the context of pathogen infection and disease and how it can potentially be exploited therapeutically, for example to improve cancer treatment.
Insights
Mitochondrial apoptosis involves pore formation, regulated by BCL-2 proteins. Sublethal mitochondrial outer membrane permeabilization (MOMP) triggers inflammation, impacting disease and cancer treatment.
Area of Science:
- Cell Biology
- Immunology
- Biochemistry
Background:
- Mitochondrial apoptosis is a key cell death pathway regulated by BCL-2 family proteins.
- Mitochondrial outer membrane permeabilization (MOMP) releases contents, activating caspases for cell death.
- Under low caspase activity, released mitochondrial factors trigger inflammatory responses.
Purpose of the Study:
- To discuss the regulation of apoptotic pore formation by BCL-2 proteins and other factors.
- To highlight the role of sublethal MOMP in mitochondrial-activated inflammation.
- To explore the physiological consequences and therapeutic potential of MOMP.
Main Methods:
- Review of BCL-2 protein family interactions.
- Analysis of cellular and mitochondrial protein involvement in pore formation.
- Examination of membrane lipid roles in MOMP.
- Discussion of inflammatory signaling pathways activated by mitochondrial release.
Main Results:
- Apoptotic pore formation is a critical regulator of mitochondrial apoptosis.
- Sublethal MOMP can initiate inflammatory responses independent of rapid cell death.
- MOMP plays a significant role in pathogen infection and various diseases.
Conclusions:
- Understanding MOMP regulation by BCL-2 proteins and other factors is crucial.
- Sublethal MOMP has significant implications for inflammation and disease pathogenesis.
- Targeting MOMP offers potential therapeutic strategies, particularly in cancer treatment.
Related Concept Videos
The Extrinsic Apoptotic Pathway
Phagocytosis of Apoptotic Cells
Normal cells contain receptors that prevent them from being recognized...
Apoptosis
The Intrinsic Apoptotic Pathway
Regulation of the Unfolded Protein Response
Caspases


