Parkin ubiquitinates Drp1 for proteasome-dependent degradation: Implication of dysregulated mitochondrial dynamics in Parkinson disease

Hongxia Wang, Pingping Song, Lei Du, Weili Tian, Wen Yue, Min Liu, Dengwen Li, Bin Wang, Yushan Zhu, Cheng Cao, Jun Zhou*, Quan Chen

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

241 Scopus citations

Abstract

Mutations in Parkin, an E3 ubiquitin ligase that regulates protein turnover, represent one of the major causes of familial Parkinson disease, a neurodegenerative disorder characterized by the loss of dopaminergic neurons and impaired mitochondrial functions. The underlying mechanism by which pathogenic Parkin mutations induce mitochondrial abnormality is not fully understood. Here, we demonstrate that Parkin interacts with and subsequently ubiquitinates dynamin-related protein 1 (Drp1), for promoting its proteasome-dependent degradation. Pathogenic mutation or knockdown of Parkin inhibits the ubiquitination and degradation of Drp1, leading to an increased level of Drp1 for mitochondrial fragmentation. These results identify Drp1 as a novel substrate of Parkin and suggest a potential mechanism linking abnormal Parkin expression to mitochondrial dysfunction in the pathogenesis of Parkinson disease.

Original languageEnglish (US)
Pages (from-to)11649-11658
Number of pages10
JournalJournal of Biological Chemistry
Volume286
Issue number13
DOIs
StatePublished - Apr 1 2011
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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