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

Publication date: Available online 11 January 2018
Source:Cell Metabolism
Author(s): Thomas G. McWilliams, Alan R. Prescott, Lambert Montava-Garriga, Graeme Ball, François Singh, Erica Barini, Miratul M.K. Muqit, Simon P. Brooks, Ian G. Ganley
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.

Graphical abstract

Teaser

The Parkinson's disease protein PINK1 is regarded as a master regulator of mitophagy. McWilliams et al. discover that endogenous PINK1 is dispensable for basal mitophagy in vivo. Furthermore, they define a rigorous framework to detect endogenous PINK1 protein in mouse tissues. This reveals the complex, context-dependent nature of mammalian mitophagy.


http://ift.tt/2DnsJIu