PINK1-dependent recruitment of Parkin to mitochondria in mitophagy

Cristofol Vives-Bauza, Chun Zhou, Yong Huang, Mei Cui, Rosa L.A. De Vries, Jiho Kim, Jessica May, Maja Aleksandra Tocilescu, Wencheng Liu, Han Seok Ko, Jordi Magrané, Darren J. Moore, Valina L. Dawson, Regis Grailhe, Ted M. Dawson, Chenjian Li, Kim Tieu, Serge Przedborski

Research output: Contribution to journalArticlepeer-review

Abstract

Phosphatase and tensin homolog (PTEN)-induced putative kinase 1 (PINK1) and PARK2/Parkin mutations cause autosomal recessive forms of Parkinson's disease. Upon a loss of mitochondrial membrane potential (Δψm) in human cells, cytosolic Parkin has been reported to be recruited to mitochondria, which is followed by a stimulation of mitochondrial autophagy. Here, we show that the relocation of Parkin to mitochondria induced by a collapse of Δψm relies on PINK1 expression and that overexpression of WT but not of mutated PINK1 causes Parkin translocation to mitochondria, even in cells with normal Δψm. We also show that once at the mitochondria, Parkin is in close proximity to PINK1, but we find no evidence that Parkin catalyzes PINK1 ubiquitination or that PINK1 phosphorylates Parkin. However, co-overexpression of Parkin and PINK1 collapses the normal tubular mitochondrial network into mitochondrial aggregates and/or large perinuclear clusters, many of which are surrounded by autophagic vacuoles. Our results suggest that Parkin, together with PINK1, modulates mitochondrial trafficking, especially to the perinuclear region, a subcellular area associated with autophagy. Thus by impairing this process, mutations in either Parkin or PINK1 may alter mitochondrial turnover which, in turn, may cause the accumulation of defective mitochondria and, ultimately, neurodegeneration in Parkinson's disease.

Original languageEnglish (US)
Pages (from-to)378-383
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume107
Issue number1
DOIs
StatePublished - 2010

Keywords

  • Autophagy
  • Parkinson's disease
  • Phosphatase and tensin homolog-induced putative kinase 1

ASJC Scopus subject areas

  • General

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