Adding Some “Splice” to Stress Eating: Autophagy, ESCRT and Alternative Splicing Orchestrate the Cellular Stress Response
Autophagy is a widely studied self-renewal pathway that is essential for degrading damaged cellular organelles or recycling biomolecules to maintain cellular homeostasis, particularly under cellular stress. This pathway initiates with formation of an autophagosome, which is a double-membrane structu...
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MDPI AG
2021-07-01
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Online Access: | https://www.mdpi.com/2073-4425/12/8/1196 |
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author | Elias Habib Allyson Cook Sabateeshan Mathavarajah Graham Dellaire |
author_facet | Elias Habib Allyson Cook Sabateeshan Mathavarajah Graham Dellaire |
author_sort | Elias Habib |
collection | DOAJ |
description | Autophagy is a widely studied self-renewal pathway that is essential for degrading damaged cellular organelles or recycling biomolecules to maintain cellular homeostasis, particularly under cellular stress. This pathway initiates with formation of an autophagosome, which is a double-membrane structure that envelopes cytosolic components and fuses with a lysosome to facilitate degradation of the contents. The endosomal sorting complexes required for transport (ESCRT) proteins play an integral role in controlling autophagosome fusion events and disruption to this machinery leads to autophagosome accumulation. Given the central role of autophagy in maintaining cellular health, it is unsurprising that dysfunction of this process is associated with many human maladies including cancer and neurodegenerative diseases. The cell can also rapidly respond to cellular stress through alternative pre-mRNA splicing that enables adaptive changes to the cell’s proteome in response to stress. Thus, alternative pre-mRNA splicing of genes that are involved in autophagy adds another layer of complexity to the cell’s stress response. Consequently, the dysregulation of alternative splicing of genes associated with autophagy and ESCRT may also precipitate disease states by either reducing the ability of the cell to respond to stress or triggering a maladaptive response that is pathogenic. In this review, we summarize the diverse roles of the ESCRT machinery and alternative splicing in regulating autophagy and how their dysfunction can have implications for human disease. |
first_indexed | 2024-03-10T08:48:19Z |
format | Article |
id | doaj.art-f6fcfbefb6464378b09614e0ccbd7dc2 |
institution | Directory Open Access Journal |
issn | 2073-4425 |
language | English |
last_indexed | 2024-03-10T08:48:19Z |
publishDate | 2021-07-01 |
publisher | MDPI AG |
record_format | Article |
series | Genes |
spelling | doaj.art-f6fcfbefb6464378b09614e0ccbd7dc22023-11-22T07:45:54ZengMDPI AGGenes2073-44252021-07-01128119610.3390/genes12081196Adding Some “Splice” to Stress Eating: Autophagy, ESCRT and Alternative Splicing Orchestrate the Cellular Stress ResponseElias Habib0Allyson Cook1Sabateeshan Mathavarajah2Graham Dellaire3Department of Pathology, Dalhousie University, Halifax, NS B3H 4R2, CanadaDepartment of Pathology, Dalhousie University, Halifax, NS B3H 4R2, CanadaDepartment of Pathology, Dalhousie University, Halifax, NS B3H 4R2, CanadaDepartment of Pathology, Dalhousie University, Halifax, NS B3H 4R2, CanadaAutophagy is a widely studied self-renewal pathway that is essential for degrading damaged cellular organelles or recycling biomolecules to maintain cellular homeostasis, particularly under cellular stress. This pathway initiates with formation of an autophagosome, which is a double-membrane structure that envelopes cytosolic components and fuses with a lysosome to facilitate degradation of the contents. The endosomal sorting complexes required for transport (ESCRT) proteins play an integral role in controlling autophagosome fusion events and disruption to this machinery leads to autophagosome accumulation. Given the central role of autophagy in maintaining cellular health, it is unsurprising that dysfunction of this process is associated with many human maladies including cancer and neurodegenerative diseases. The cell can also rapidly respond to cellular stress through alternative pre-mRNA splicing that enables adaptive changes to the cell’s proteome in response to stress. Thus, alternative pre-mRNA splicing of genes that are involved in autophagy adds another layer of complexity to the cell’s stress response. Consequently, the dysregulation of alternative splicing of genes associated with autophagy and ESCRT may also precipitate disease states by either reducing the ability of the cell to respond to stress or triggering a maladaptive response that is pathogenic. In this review, we summarize the diverse roles of the ESCRT machinery and alternative splicing in regulating autophagy and how their dysfunction can have implications for human disease.https://www.mdpi.com/2073-4425/12/8/1196autophagyESCRTalternative splicingcancerneurodegenerative and eye disease |
spellingShingle | Elias Habib Allyson Cook Sabateeshan Mathavarajah Graham Dellaire Adding Some “Splice” to Stress Eating: Autophagy, ESCRT and Alternative Splicing Orchestrate the Cellular Stress Response Genes autophagy ESCRT alternative splicing cancer neurodegenerative and eye disease |
title | Adding Some “Splice” to Stress Eating: Autophagy, ESCRT and Alternative Splicing Orchestrate the Cellular Stress Response |
title_full | Adding Some “Splice” to Stress Eating: Autophagy, ESCRT and Alternative Splicing Orchestrate the Cellular Stress Response |
title_fullStr | Adding Some “Splice” to Stress Eating: Autophagy, ESCRT and Alternative Splicing Orchestrate the Cellular Stress Response |
title_full_unstemmed | Adding Some “Splice” to Stress Eating: Autophagy, ESCRT and Alternative Splicing Orchestrate the Cellular Stress Response |
title_short | Adding Some “Splice” to Stress Eating: Autophagy, ESCRT and Alternative Splicing Orchestrate the Cellular Stress Response |
title_sort | adding some splice to stress eating autophagy escrt and alternative splicing orchestrate the cellular stress response |
topic | autophagy ESCRT alternative splicing cancer neurodegenerative and eye disease |
url | https://www.mdpi.com/2073-4425/12/8/1196 |
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