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

Thomas G. McWilliams (Lead / Corresponding author), Alan R. Prescott, Lambert Montava-Garriga, Graeme Ball, François Singh, Erica Barini, Miratul M. K. Muqit, Simon P. Brooks, Ian G. Ganley (Lead / Corresponding author)

Research output: Contribution to journalArticle

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Abstract

Dysregulated mitophagy has been linked to Parkinson’s disease (PD) due to the role of 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 orchestrate mammalian mitochondrial integrity in a contextdependent fashion, and this has profound implications for our molecular understanding of vertebrate mitophagy.
Original languageEnglish
Pages (from-to)439-449.e5
Number of pages17
JournalCell Metabolism
Volume27
Issue number2
Early online date11 Jan 2018
DOIs
Publication statusPublished - 6 Feb 2018

Fingerprint

Mitochondrial Degradation
Parkinson Disease
Dopaminergic Neurons
Microglia
Islets of Langerhans
Vertebrates

Keywords

  • Autophagy
  • Dopaminergic
  • Mitochondria
  • Mitophagy
  • Neurodegeneration
  • Pancreas
  • Parkinson's disease
  • PINK1
  • Retina

Cite this

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title = "Basal Mitophagy Occurs Independently of PINK1 in Mouse Tissues of High Metabolic Demand",
abstract = "Dysregulated mitophagy has been linked to Parkinson’s disease (PD) due to the role of 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 orchestrate mammalian mitochondrial integrity in a contextdependent fashion, and this has profound implications for our molecular understanding of vertebrate mitophagy.",
keywords = "Autophagy, Dopaminergic, Mitochondria, Mitophagy, Neurodegeneration, Pancreas, Parkinson's disease, PINK1, Retina",
author = "McWilliams, {Thomas G.} and Prescott, {Alan R.} and Lambert Montava-Garriga and Graeme Ball and Fran{\cc}ois Singh and Erica Barini and Muqit, {Miratul M. K.} and Brooks, {Simon P.} and Ganley, {Ian G.}",
note = "This work was primarily funded by an MRC grant (MC_UU_12016/4) and an MJFF grant (11470). A co-author (Miratul Muqit) is also funded by Wellcome (101022/Z/13/Z).",
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Basal Mitophagy Occurs Independently of PINK1 in Mouse Tissues of High Metabolic Demand. / McWilliams, Thomas G. (Lead / Corresponding author); Prescott, Alan R.; Montava-Garriga, Lambert; Ball, Graeme; Singh, François; Barini, Erica; Muqit, Miratul M. K.; Brooks, Simon P. ; Ganley, Ian G. (Lead / Corresponding author).

In: Cell Metabolism, Vol. 27, No. 2, 06.02.2018, p. 439-449.e5.

Research output: Contribution to journalArticle

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AU - Singh, François

AU - Barini, Erica

AU - Muqit, Miratul M. K.

AU - Brooks, Simon P.

AU - Ganley, Ian G.

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