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Cell Metab. 2018 Feb 6;27(2):439-449.e5. doi: 10.1016/j.cmet.2017.12.008. Epub 2018 Jan 11.

Basal Mitophagy Occurs Independently of PINK1 in Mouse Tissues of High Metabolic Demand.

Author information

1
MRC Protein Phosphorylation and Ubiquitylation Unit, University of Dundee, Dundee DD1 5EH, UK. Electronic address: thomas.mcwilliams@helsinki.fi.
2
Dundee Imaging Facility, School of Life Sciences, University of Dundee, Dundee DD1 5EH, UK.
3
MRC Protein Phosphorylation and Ubiquitylation Unit, University of Dundee, Dundee DD1 5EH, UK.
4
MRC Protein Phosphorylation and Ubiquitylation Unit, University of Dundee, Dundee DD1 5EH, UK; School of Medicine, University of Dundee, Dundee, DD1 9SY, UK.
5
The Brain Repair Group, Division of Neuroscience, School of Biosciences, Cardiff University, Cardiff CF10 3AX, UK.
6
MRC Protein Phosphorylation and Ubiquitylation Unit, University of Dundee, Dundee DD1 5EH, UK. Electronic address: i.ganley@dundee.ac.uk.

Abstract

Dysregulated mitophagy has been linked to Parkinson's disease (PD) due to the role of PTEN-induced kinase 1 (PINK1) in mediating depolarization-induced mitophagy in vitro. Elegant mouse reporters have revealed the pervasive nature of basal mitophagy in vivo, yet the role of PINK1 and tissue metabolic context remains unknown. Using mito-QC, we investigated the contribution of PINK1 to mitophagy in metabolically active tissues. We observed a high degree of mitophagy in neural cells, including PD-relevant mesencephalic dopaminergic neurons and microglia. In all tissues apart from pancreatic islets, loss of Pink1 did not influence basal mitophagy, despite disrupting depolarization-induced Parkin activation. Our findings provide the first in vivo evidence that PINK1 is detectable at basal levels and that basal mammalian mitophagy occurs independently of PINK1. This suggests multiple, yet-to-be-discovered pathways orchestrating mammalian mitochondrial integrity in a context-dependent fashion, and this has profound implications for our molecular understanding of vertebrate mitophagy.

KEYWORDS:

PINK1; Parkinson's disease; autophagy; dopaminergic; mitochondria; mitophagy; neurodegeneration; pancreas; retina

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