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Basal mitophagy is widespread in Drosophila but minimally affected by loss of Pink1 or parkin

The Parkinson’s disease factors PINK1 and parkin are strongly implicated in stress-induced mitophagy in vitro, but little is known about their impact on basal mitophagy in vivo. We generated transgenic Drosophila melanogaster expressing fluorescent mitophagy reporters to evaluate the impact of Pink1...

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Autores principales: Lee, Juliette J., Sanchez-Martinez, Alvaro, Zarate, Aitor Martinez, Benincá, Cristiane, Mayor, Ugo, Clague, Michael J., Whitworth, Alexander J.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Rockefeller University Press 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5940313/
https://www.ncbi.nlm.nih.gov/pubmed/29500189
http://dx.doi.org/10.1083/jcb.201801044
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author Lee, Juliette J.
Sanchez-Martinez, Alvaro
Zarate, Aitor Martinez
Benincá, Cristiane
Mayor, Ugo
Clague, Michael J.
Whitworth, Alexander J.
author_facet Lee, Juliette J.
Sanchez-Martinez, Alvaro
Zarate, Aitor Martinez
Benincá, Cristiane
Mayor, Ugo
Clague, Michael J.
Whitworth, Alexander J.
author_sort Lee, Juliette J.
collection PubMed
description The Parkinson’s disease factors PINK1 and parkin are strongly implicated in stress-induced mitophagy in vitro, but little is known about their impact on basal mitophagy in vivo. We generated transgenic Drosophila melanogaster expressing fluorescent mitophagy reporters to evaluate the impact of Pink1/parkin mutations on basal mitophagy under physiological conditions. We find that mitophagy is readily detectable and abundant in many tissues, including Parkinson’s disease–relevant dopaminergic neurons. However, we did not detect mitolysosomes in flight muscle. Surprisingly, in Pink1 or parkin null flies, we did not observe any substantial impact on basal mitophagy. Because these flies exhibit locomotor defects and dopaminergic neuron loss, our findings raise questions about current assumptions of the pathogenic mechanism associated with the PINK1/parkin pathway. Our findings provide evidence that Pink1 and parkin are not essential for bulk basal mitophagy in Drosophila. They also emphasize that mechanisms underpinning basal mitophagy remain largely obscure.
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spelling pubmed-59403132018-05-10 Basal mitophagy is widespread in Drosophila but minimally affected by loss of Pink1 or parkin Lee, Juliette J. Sanchez-Martinez, Alvaro Zarate, Aitor Martinez Benincá, Cristiane Mayor, Ugo Clague, Michael J. Whitworth, Alexander J. J Cell Biol Research Articles The Parkinson’s disease factors PINK1 and parkin are strongly implicated in stress-induced mitophagy in vitro, but little is known about their impact on basal mitophagy in vivo. We generated transgenic Drosophila melanogaster expressing fluorescent mitophagy reporters to evaluate the impact of Pink1/parkin mutations on basal mitophagy under physiological conditions. We find that mitophagy is readily detectable and abundant in many tissues, including Parkinson’s disease–relevant dopaminergic neurons. However, we did not detect mitolysosomes in flight muscle. Surprisingly, in Pink1 or parkin null flies, we did not observe any substantial impact on basal mitophagy. Because these flies exhibit locomotor defects and dopaminergic neuron loss, our findings raise questions about current assumptions of the pathogenic mechanism associated with the PINK1/parkin pathway. Our findings provide evidence that Pink1 and parkin are not essential for bulk basal mitophagy in Drosophila. They also emphasize that mechanisms underpinning basal mitophagy remain largely obscure. Rockefeller University Press 2018-05-07 /pmc/articles/PMC5940313/ /pubmed/29500189 http://dx.doi.org/10.1083/jcb.201801044 Text en © 2018 University of Cambridge https://creativecommons.org/licenses/by/4.0/This article is available under a Creative Commons License (Attribution 4.0 International, as described at https://creativecommons.org/licenses/by/4.0/).
spellingShingle Research Articles
Lee, Juliette J.
Sanchez-Martinez, Alvaro
Zarate, Aitor Martinez
Benincá, Cristiane
Mayor, Ugo
Clague, Michael J.
Whitworth, Alexander J.
Basal mitophagy is widespread in Drosophila but minimally affected by loss of Pink1 or parkin
title Basal mitophagy is widespread in Drosophila but minimally affected by loss of Pink1 or parkin
title_full Basal mitophagy is widespread in Drosophila but minimally affected by loss of Pink1 or parkin
title_fullStr Basal mitophagy is widespread in Drosophila but minimally affected by loss of Pink1 or parkin
title_full_unstemmed Basal mitophagy is widespread in Drosophila but minimally affected by loss of Pink1 or parkin
title_short Basal mitophagy is widespread in Drosophila but minimally affected by loss of Pink1 or parkin
title_sort basal mitophagy is widespread in drosophila but minimally affected by loss of pink1 or parkin
topic Research Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5940313/
https://www.ncbi.nlm.nih.gov/pubmed/29500189
http://dx.doi.org/10.1083/jcb.201801044
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