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PINK1 and parkin shape the organism-wide distribution of a deleterious mitochondrial genome

Arnaud Ahier, Nadia Cummins, Chuan-Yang Dai, Jürgen Götz, View ORCID ProfileSteven Zuryn
doi: https://doi.org/10.1101/576165
Arnaud Ahier
1Clem Jones Centre for Ageing Dementia Research, Queensland Brain Institute, The University of Queensland, Brisbane, Australia, 4072
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Nadia Cummins
1Clem Jones Centre for Ageing Dementia Research, Queensland Brain Institute, The University of Queensland, Brisbane, Australia, 4072
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Chuan-Yang Dai
1Clem Jones Centre for Ageing Dementia Research, Queensland Brain Institute, The University of Queensland, Brisbane, Australia, 4072
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Jürgen Götz
1Clem Jones Centre for Ageing Dementia Research, Queensland Brain Institute, The University of Queensland, Brisbane, Australia, 4072
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Steven Zuryn
1Clem Jones Centre for Ageing Dementia Research, Queensland Brain Institute, The University of Queensland, Brisbane, Australia, 4072
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  • ORCID record for Steven Zuryn
  • For correspondence: s.zuryn@uq.edu.au
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Abstract

In multiple species, certain tissue types are prone to acquiring greater loads of mitochondrial genome (mtDNA) mutations relative to others, however the mechanisms that drive these heteroplasmy differences are unknown. We found that the conserved PTEN-induced putative kinase (PINK1/PINK-1) and the E3 ubiquitin-protein ligase parkin (PDR-1), which are required for mitochondrial autophagy (mitophagy), underlie stereotyped differences in heteroplasmy of a deleterious mitochondrial genome mutation (ΔmtDNA) between major somatic tissues types in Caenorhabditis elegans. We demonstrate that tissues prone to accumulating ΔmtDNA have lower mitophagy responses than those with low mutation levels, such as neurons. Moreover, we show that ΔmtDNA heteroplasmy increases when proteotoxic species that are associated with neurodegenerative disease and mitophagy inhibition are overexpressed in the nervous system. Together, these results suggest that PINK1 and parkin drive organism-wide patterns of heteroplasmy and provide evidence of a causal link between proteotoxicity, mitophagy, and mtDNA mutation levels in neurons.

Competing Interest Statement

The authors have declared no competing interest.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission.
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Posted June 12, 2020.
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PINK1 and parkin shape the organism-wide distribution of a deleterious mitochondrial genome
Arnaud Ahier, Nadia Cummins, Chuan-Yang Dai, Jürgen Götz, Steven Zuryn
bioRxiv 576165; doi: https://doi.org/10.1101/576165
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PINK1 and parkin shape the organism-wide distribution of a deleterious mitochondrial genome
Arnaud Ahier, Nadia Cummins, Chuan-Yang Dai, Jürgen Götz, Steven Zuryn
bioRxiv 576165; doi: https://doi.org/10.1101/576165

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