Deficiency of parkin and PINK1 impairs age-dependent mitophagy in Drosophila

Elife. 2018 May 29;7:e35878. doi: 10.7554/eLife.35878.

Abstract

Mutations in the genes for PINK1 and parkin cause Parkinson's disease. PINK1 and parkin cooperate in the selective autophagic degradation of damaged mitochondria (mitophagy) in cultured cells. However, evidence for their role in mitophagy in vivo is still scarce. Here, we generated a Drosophila model expressing the mitophagy probe mt-Keima. Using live mt-Keima imaging and correlative light and electron microscopy (CLEM), we show that mitophagy occurs in muscle cells and dopaminergic neurons in vivo, even in the absence of exogenous mitochondrial toxins. Mitophagy increases with aging, and this age-dependent rise is abrogated by PINK1 or parkin deficiency. Knockdown of the Drosophila homologues of the deubiquitinases USP15 and, to a lesser extent, USP30, rescues mitophagy in the parkin-deficient flies. These data demonstrate a crucial role for parkin and PINK1 in age-dependent mitophagy in Drosophila in vivo.

Keywords: D. melanogaster; Parkinson's disease; USP15; USP30; aging; autophagy; cell biology; human biology; medicine; mitochondria.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aging*
  • Animals
  • Autophagy*
  • Dopaminergic Neurons / metabolism
  • Dopaminergic Neurons / pathology
  • Drosophila Proteins / genetics
  • Drosophila Proteins / metabolism*
  • Drosophila melanogaster / cytology
  • Drosophila melanogaster / metabolism
  • Drosophila melanogaster / physiology*
  • Mitochondria / metabolism
  • Mitochondria / pathology*
  • Mitophagy
  • Muscle, Skeletal / metabolism
  • Muscle, Skeletal / pathology
  • Protein-Serine-Threonine Kinases / genetics
  • Protein-Serine-Threonine Kinases / metabolism*
  • Ubiquitin-Protein Ligases / genetics
  • Ubiquitin-Protein Ligases / metabolism*

Substances

  • Drosophila Proteins
  • Ubiquitin-Protein Ligases
  • PINK1 protein, Drosophila
  • Protein-Serine-Threonine Kinases
  • park protein, Drosophila

Grant support

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.