Deficiency of parkin and PINK1 impairs age-dependent mitophagy in Drosophila
- KU Leuven, Belgium
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.
Data availability
All data generated or analysed during this study are included in the manuscript and supporting files. Source data files have been provided for Figures 1, 3 and 4.
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Author details
Funding
Research Foundation - Flanders (1500817N)
- Tom Cornelissen
KU Leuven
- Wim Vandenberghe
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Copyright
© 2018, Cornelissen et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Deficiency of parkin and PINK1 impairs age-dependent mitophagy in Drosophila
eLife 7:e35878.
https://doi.org/10.7554/eLife.35878
