Molecular crosstalk between apoptosis, necroptosis, and survival signaling
Tom Vanden Berghe1, William J Kaiser2, Mathieu Jm Bertrand1
1Inflammation Research Center; VIB; Ghent, Belgium; Department of Biomedical Molecular Biological; Ghent University; Ghent, Belgium.
Abstract:
Our current knowledge of the molecular mechanisms regulating the signaling pathways leading to cell survival, cell death, and inflammation has shed light on the tight mutual interplays between these processes. Moreover, the fact that both apoptosis and necrosis can be molecularly controlled has greatly increased our interest in the roles that these types of cell death play in the control of general processes such as development, homeostasis, and inflammation. In this review, we provide a brief update on the different cell death modalities and describe in more detail the intracellular crosstalk between survival, apoptotic, necroptotic, and inflammatory pathways that are activated downstream of death receptors. An important concept is that the different cell death processes modulate each other by mutual inhibitory mechanisms, serve as alternative back-up death routes in the case of a defect in the first-line cell death response, and are controlled by multiple feedback loops. We conclude by discussing future perspectives and challenges in the field of cell death and inflammation research.
Insights
Cell death processes like apoptosis and necrosis are tightly regulated and interconnected with survival and inflammation pathways. Understanding these molecular interactions is crucial for controlling development, homeostasis, and inflammatory responses.
Area of Science:
- Molecular Biology
- Immunology
- Cell Biology
Background:
- Cell survival, death, and inflammation are intricately linked molecular processes.
- Apoptosis and necrosis are now understood to be molecularly controllable.
- Cell death plays critical roles in development, homeostasis, and inflammation.
Purpose of the Study:
- To review current knowledge on cell death modalities.
- To detail the intracellular crosstalk between survival, apoptotic, necroptotic, and inflammatory pathways.
- To highlight the regulatory mechanisms governing cell death and inflammation.
Main Methods:
- Literature review of molecular mechanisms.
- Analysis of intracellular signaling pathways downstream of death receptors.
- Discussion of regulatory feedback loops and interconnections.
Main Results:
- Cell death modalities (apoptosis, necrosis) are molecularly controlled and interconnected.
- Intracellular crosstalk exists between survival, apoptotic, necroptotic, and inflammatory pathways.
- Mutual inhibition, backup routes, and feedback loops regulate cell death processes.
Conclusions:
- Cell death and inflammation research is a rapidly evolving field.
- Future research should focus on the complex interplay and regulatory networks.
- Understanding these pathways has implications for various physiological and pathological processes.
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