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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Main Authors: Elias Habib, Allyson Cook, Sabateeshan Mathavarajah, Graham Dellaire
Format: Article
Language:English
Published: MDPI AG 2021-07-01
Series:Genes
Subjects:
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.
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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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