PINK1 protects against cell death induced by mitochondrial depolarization, by phosphorylating Bcl-xL and impairing its pro-apoptotic cleavage

G. Arena, V. Gelmetti, L. Torosantucci, D. Vignone, G. Lamorte, P. De Rosa, E. Cilia, E. A. Jonas, E. M. Valente

Research output: Contribution to journalArticle

Abstract

Mutations in the PINK1 gene are a frequent cause of autosomal recessive Parkinson's disease (PD). PINK1 encodes a mitochondrial kinase with neuroprotective activity, implicated in maintaining mitochondrial homeostasis and function. In concurrence with Parkin, PINK1 regulates mitochondrial trafficking and degradation of damaged mitochondria through mitophagy. Moreover, PINK1 can activate autophagy by interacting with the pro-autophagic protein Beclin-1. Here, we report that, upon mitochondrial depolarization, PINK1 interacts with and phosphorylates Bcl-xL, an anti-apoptotic protein also known to inhibit autophagy through its binding to Beclin-1. PINK1-Bcl-xL interaction does not interfere either with Beclin-1 release from Bcl-xL or the mitophagy pathway; rather it protects against cell death by hindering the pro-apoptotic cleavage of Bcl-xL. Our data provide a functional link between PINK1, Bcl-xL and apoptosis, suggesting a novel mechanism through which PINK1 regulates cell survival. This pathway could be relevant for the pathogenesis of PD as well as other diseases including cancer.

Original languageEnglish
Pages (from-to)920-930
Number of pages11
JournalCell Death and Differentiation
Volume20
Issue number7
DOIs
Publication statusPublished - Jul 2013

Fingerprint

Mitochondrial Degradation
Cell Death
Autophagy
Parkinson Disease
Apoptosis Regulatory Proteins
Cell Survival
Mitochondria
Homeostasis
Phosphotransferases
Apoptosis
Mutation
Genes
Beclin-1
Neoplasms

Keywords

  • Apoptosis
  • Mitochondria
  • Parkinson's disease
  • Post-translational modifications

ASJC Scopus subject areas

  • Cell Biology
  • Molecular Biology

Cite this

PINK1 protects against cell death induced by mitochondrial depolarization, by phosphorylating Bcl-xL and impairing its pro-apoptotic cleavage. / Arena, G.; Gelmetti, V.; Torosantucci, L.; Vignone, D.; Lamorte, G.; De Rosa, P.; Cilia, E.; Jonas, E. A.; Valente, E. M.

In: Cell Death and Differentiation, Vol. 20, No. 7, 07.2013, p. 920-930.

Research output: Contribution to journalArticle

Arena, G. ; Gelmetti, V. ; Torosantucci, L. ; Vignone, D. ; Lamorte, G. ; De Rosa, P. ; Cilia, E. ; Jonas, E. A. ; Valente, E. M. / PINK1 protects against cell death induced by mitochondrial depolarization, by phosphorylating Bcl-xL and impairing its pro-apoptotic cleavage. In: Cell Death and Differentiation. 2013 ; Vol. 20, No. 7. pp. 920-930.
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