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

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

Author information

1
Laboratory for Parkinson Research, Department of Neurosciences, Leuven, Belgium.
2
Department of Neurosciences, KU Leuven, Leuven, Belgium.
3
VIB-KU Leuven Center for Brain & Disease Research, Leuven, Belgium.
4
VIB Electron Microscopy Platform and BioImaging Core, Department of Neurosciences, VIB-KU Leuven Center for Brain and Disease Research, KU Leuven, Leuven, Belgium.
5
Department of Neurology, University Hospitals Leuven, 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.

KEYWORDS:

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

Comment in

PMID:
29809156
PMCID:
PMC6008047
DOI:
10.7554/eLife.35878
[Indexed for MEDLINE]
Free PMC Article

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