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

Authors
  • Brunelli, Francesco1
  • Torosantucci, Liliana2
  • Gelmetti, Vania2
  • Franzone, Davide1
  • Grünewald, Anne3, 4
  • Krüger, Rejko3, 5, 6
  • Arena, Giuseppe3
  • Valente, Enza Maria1, 7
  • 1 Department of Molecular Medicine, University of Pavia, 27100 Pavia, Italy. , (Italy)
  • 2 Mendel Laboratory, Casa Sollievo della Sofferenza Hospital, IRCCS, 71013 San Giovanni Rotondo, Italy. , (Italy)
  • 3 Luxembourg Centre for Systems Biomedicine, University of Luxembourg, L-4367 Luxembourg, Luxembourg. , (Luxembourg)
  • 4 Institute of Neurogenetics, University of Lübeck, 23538 Lubeck, Germany. , (Germany)
  • 5 Centre Hospitalier du Luxembourg, Parkinson Research Clinic, L-1210 Luxembourg, Luxembourg. , (Luxembourg)
  • 6 Transversal Translational Medicine, Luxembourg Institute of Health, L-1445 Luxembourg, Luxembourg. , (Luxembourg)
  • 7 Neurogenetics Research Centre, IRCCS Mondino Foundation, 27100 Pavia, Italy. , (Italy)
Type
Published Article
Journal
Cells
Publisher
MDPI AG
Publication Date
Feb 15, 2022
Volume
11
Issue
4
Identifiers
DOI: 10.3390/cells11040678
PMID: 35203326
Source
Medline
Keywords
Language
English
License
Unknown

Abstract

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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