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PINK1 Protects against Staurosporine-Induced Apoptosis by Interacting with Beclin1 and Impairing Its Pro-Apoptotic Cleavage

PINK1 is a causative gene for Parkinson’s disease and the corresponding protein has been identified as a master regulator of mitophagy—the autophagic degradation of damaged mitochondria. It interacts with Beclin1 to regulate autophagy and initiate autophagosome formation, even outside the context of...

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Autores principales: Brunelli, Francesco, Torosantucci, Liliana, Gelmetti, Vania, Franzone, Davide, Grünewald, Anne, Krüger, Rejko, Arena, Giuseppe, Valente, Enza Maria
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8870463/
https://www.ncbi.nlm.nih.gov/pubmed/35203326
http://dx.doi.org/10.3390/cells11040678
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author Brunelli, Francesco
Torosantucci, Liliana
Gelmetti, Vania
Franzone, Davide
Grünewald, Anne
Krüger, Rejko
Arena, Giuseppe
Valente, Enza Maria
author_facet Brunelli, Francesco
Torosantucci, Liliana
Gelmetti, Vania
Franzone, Davide
Grünewald, Anne
Krüger, Rejko
Arena, Giuseppe
Valente, Enza Maria
author_sort Brunelli, Francesco
collection PubMed
description PINK1 is a causative gene for Parkinson’s disease and the corresponding protein has been identified as a master regulator of mitophagy—the autophagic degradation of damaged mitochondria. It interacts with Beclin1 to regulate autophagy and initiate autophagosome formation, even outside the context of mitophagy. Several other pro-survival functions of this protein have been described and indicate that it might play a role in other disorders, such as cancer and proliferative diseases. In this study, we investigated a novel anti-apoptotic function of PINK1. To do so, we used SH-SY5Y neuroblastoma cells, a neuronal model used in Parkinson’s disease and cancer studies, to characterize the pro-survival functions of PINK1 in response to the apoptosis inducer staurosporine. In this setting, we found that staurosporine induces apoptosis but not mitophagy, and we demonstrated that PINK1 protects against staurosporine-induced apoptosis by impairing the pro-apoptotic cleavage of Beclin1. Our data also show that staurosporine-induced apoptosis is preceded by a phase of enhanced autophagy, and that PINK1 in this context regulates the switch from autophagy to apoptosis. PINK1 protein levels progressively decrease after treatment, inducing this switch. The PINK1–Beclin1 interaction is crucial in exerting this function, as mutants that are unable to interact do not show the anti-apoptotic effect. We characterized a new anti-apoptotic function of PINK1 that could provide options for treatment in proliferative or neurodegenerative diseases.
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spelling pubmed-88704632022-02-25 PINK1 Protects against Staurosporine-Induced Apoptosis by Interacting with Beclin1 and Impairing Its Pro-Apoptotic Cleavage Brunelli, Francesco Torosantucci, Liliana Gelmetti, Vania Franzone, Davide Grünewald, Anne Krüger, Rejko Arena, Giuseppe Valente, Enza Maria Cells Article PINK1 is a causative gene for Parkinson’s disease and the corresponding protein has been identified as a master regulator of mitophagy—the autophagic degradation of damaged mitochondria. It interacts with Beclin1 to regulate autophagy and initiate autophagosome formation, even outside the context of mitophagy. Several other pro-survival functions of this protein have been described and indicate that it might play a role in other disorders, such as cancer and proliferative diseases. In this study, we investigated a novel anti-apoptotic function of PINK1. To do so, we used SH-SY5Y neuroblastoma cells, a neuronal model used in Parkinson’s disease and cancer studies, to characterize the pro-survival functions of PINK1 in response to the apoptosis inducer staurosporine. In this setting, we found that staurosporine induces apoptosis but not mitophagy, and we demonstrated that PINK1 protects against staurosporine-induced apoptosis by impairing the pro-apoptotic cleavage of Beclin1. Our data also show that staurosporine-induced apoptosis is preceded by a phase of enhanced autophagy, and that PINK1 in this context regulates the switch from autophagy to apoptosis. PINK1 protein levels progressively decrease after treatment, inducing this switch. The PINK1–Beclin1 interaction is crucial in exerting this function, as mutants that are unable to interact do not show the anti-apoptotic effect. We characterized a new anti-apoptotic function of PINK1 that could provide options for treatment in proliferative or neurodegenerative diseases. MDPI 2022-02-15 /pmc/articles/PMC8870463/ /pubmed/35203326 http://dx.doi.org/10.3390/cells11040678 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Brunelli, Francesco
Torosantucci, Liliana
Gelmetti, Vania
Franzone, Davide
Grünewald, Anne
Krüger, Rejko
Arena, Giuseppe
Valente, Enza Maria
PINK1 Protects against Staurosporine-Induced Apoptosis by Interacting with Beclin1 and Impairing Its Pro-Apoptotic Cleavage
title PINK1 Protects against Staurosporine-Induced Apoptosis by Interacting with Beclin1 and Impairing Its Pro-Apoptotic Cleavage
title_full PINK1 Protects against Staurosporine-Induced Apoptosis by Interacting with Beclin1 and Impairing Its Pro-Apoptotic Cleavage
title_fullStr PINK1 Protects against Staurosporine-Induced Apoptosis by Interacting with Beclin1 and Impairing Its Pro-Apoptotic Cleavage
title_full_unstemmed PINK1 Protects against Staurosporine-Induced Apoptosis by Interacting with Beclin1 and Impairing Its Pro-Apoptotic Cleavage
title_short PINK1 Protects against Staurosporine-Induced Apoptosis by Interacting with Beclin1 and Impairing Its Pro-Apoptotic Cleavage
title_sort pink1 protects against staurosporine-induced apoptosis by interacting with beclin1 and impairing its pro-apoptotic cleavage
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8870463/
https://www.ncbi.nlm.nih.gov/pubmed/35203326
http://dx.doi.org/10.3390/cells11040678
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