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Lighting Up the Pathways to Caspase Activation Using Bimolecular Fluorescence Complementation
Published on: March 5, 2018
Caspase involvement in autophagy
Panagiotis Tsapras1, Ioannis P Nezis1
1School of Life Sciences, University of Warwick, Coventry CV4 7AL, UK.
Abstract:
Caspases are a family of cysteine proteases widely known as the principal mediators of the apoptotic cell death response, but considerably less so as the contributors to the regulation of pathways outside cellular demise. In regards to autophagy, the modulatory roles of caspases have only recently begun to be adequately described. In contrast to apoptosis, autophagy promotes cell survival by providing energy and nutrients through the lysosomal degradation of cytoplasmic constituents. Under basal conditions autophagy and apoptosis cross-regulate each other through an elaborate network of interconnections which also includes the interplay between autophagy-related proteins (ATGs) and caspases. In this review we focus on the effects of this crosstalk at the cellular level, as we aim to concentrate the main observations from research conducted so far on the fine-tuning of autophagy by caspases. Several members of this protease-family have been found to directly interact with key ATGs involved in different tiers across the autophagic cascade. Therefore, we firstly outline the core mechanism of macroautophagy in brief. In an effort to emphasize the importance of the intricate cross-regulation of ATGs and caspases, we also present examples of autophagy's contribution to apoptotic cell death during development.
Insights
Caspases (cysteine proteases) fine-tune autophagy, a cell survival process, by interacting with autophagy-related proteins (ATGs). This crosstalk reveals new insights into cellular regulation beyond apoptosis.
Area of Science:
- Molecular Biology
- Cell Biology
- Biochemistry
Background:
- Caspases are key mediators of apoptosis (programmed cell death).
- Their role in regulating autophagy, a cell survival pathway, is less understood.
- Autophagy and apoptosis are interconnected pathways involving autophagy-related proteins (ATGs) and caspases.
Purpose of the Study:
- To review the cellular-level effects of crosstalk between caspases and autophagy.
- To highlight the fine-tuning of autophagy by caspases.
- To examine interactions between caspases and key autophagy-related proteins (ATGs).
Main Methods:
- Literature review focusing on research into caspase-autophagy crosstalk.
- Analysis of studies detailing direct interactions between caspases and ATGs.
- Brief outline of the core mechanism of macroautophagy.
Main Results:
- Caspases directly interact with critical ATGs across the autophagic cascade.
- This interaction modulates the process of autophagy.
- Autophagy can contribute to apoptotic cell death during development.
Conclusions:
- Caspases play a significant role in regulating autophagy, impacting cell survival.
- The intricate cross-regulation between ATGs and caspases is crucial for cellular homeostasis.
- Understanding this crosstalk provides new perspectives on cell death and survival pathways.
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