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

Cell metabolism | 2018

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.

Pubmed ID: 29337137 RIS Download

Associated grants

  • Agency: Medical Research Council, United Kingdom
    Id: MC_UU_12016/4
  • Agency: Medical Research Council, United Kingdom
    Id: MC_UU_00018/2
  • Agency: Wellcome Trust, United Kingdom
    Id: 097945/B/11/Z
  • Agency: Wellcome Trust, United Kingdom
  • Agency: Medical Research Council, United Kingdom
    Id: MR/K015869/1
  • Agency: Wellcome Trust, United Kingdom
    Id: 101022/Z/13/Z

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This is a list of tools and resources that we have found mentioned in this publication.


Thermo Fisher Scientific (tool)

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Molecular Probes (tool)

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Wako (tool)

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Mus musculus with name C57BL/6Smoc-Pink1em1Smoc from IMSR.

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C57BL/6J (tool)

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C57BL/6J (tool)

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Vinculin antibody [EPR8185] (antibody)

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MatrixScience (software resource)

RRID:SCR_000307

A collection of both commercial and noncommercial software products which includes: Mascot Distiller, Mascot Parser, and Mascot Server. Mascot Distiller is commercial and provides a single interface to process raw data into de-isotoped peak lists. This tool can also be used for the easy distribution of search and quantitative results to colleagues. The non-commercial Mascot Parser software provides an API (Application Programmer Interface) that makes it easier to access search results written in C++, Java, Python and Perl. Mascot Server is non-commercial, and is a collection of peptide mass fingerprints as well as a MS/MS database. A selection of popular sequence databases are available online and include SwissProt, NCBInr, and the EST divisions of EMBL. This server is best used for evaluating and searching for smaller data sets.

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ATPB antibody [3D5] - Mitochondrial Marker (antibody)

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