Deciphering the molecular signals of PINK1/Parkin mitophagy

Thanh N. Nguyen, Benjamin S. Padman, Michael Lazarou

Research output: Contribution to journalReview ArticleOtherpeer-review

182 Citations (Scopus)

Abstract

Functional mitochondria are critically important for the maintenance of cellular integrity and survival. Mitochondrial dysfunction is a major contributor to neurodegenerative diseases including Parkinson's disease (PD). Two gene products mutated in familial Parkinsonism, PINK1 and Parkin, function together to degrade damaged mitochondria through a selective form of autophagy termed mitophagy. PINK1 accumulates on the surface of dysfunctional mitochondria where it simultaneously recruits and activates Parkin's E3 ubiquitin ligase activity. This forms the basis of multiple signaling events that culminate in engulfment of damaged mitochondria within autophagosomes and degradation by lysosomes. This review discusses the molecular signals of PINK1/Parkin mitophagy and the ubiquitin code that drives not only Parkin recruitment and activation by PINK1 but also the downstream signaling events of mitophagy.
Original languageEnglish
Pages (from-to)733-744
Number of pages12
JournalTrends in Cell Biology
Volume26
Issue number10
DOIs
Publication statusPublished - Oct 2016

Keywords

  • Autophagy
  • Mitophagy
  • Parkin
  • Parkinson's disease
  • PINK1
  • ubiquitin

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