Basal mitophagy occurs independently of PINK1 in mouse tissues of high metabolic demand

McWilliams, Thomas G., Prescott, Alan R., Montava-Garriga, Lambert, Ball, Graeme, Singh, Francois, Barini, Erica, Muqit, Miratul M. K., Brooks, Simon P. ORCID: https://orcid.org/0000-0001-9853-6177 and Ganley, Ian G. 2018. Basal mitophagy occurs independently of PINK1 in mouse tissues of high metabolic demand. Cell Metabolism 27 (2) , 439-449.e5. 10.1016/j.cmet.2017.12.008

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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 PDrelevant 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-tobe- discovered pathways orchestrating mammalian mitochondrial integrity in a context-dependent fashion, and this has profound implications for our molecular understanding of vertebrate mitophagy.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Medicine Biosciences
Subjects:	R Medicine > RC Internal medicine > RC0321 Neuroscience. Biological psychiatry. Neuropsychiatry
Additional Information:	This is an open access article under the terms of the CC-BY license.
Publisher:	Elsevier
ISSN:	1550-4131
Date of First Compliant Deposit:	19 March 2018
Date of Acceptance:	12 December 2017
Last Modified:	05 May 2023 13:21
URI:	https://orca.cardiff.ac.uk/id/eprint/109968

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