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Inhibition of the deubiquitinase USP8 corrects a Drosophila PINK1 model of mitochondria dysfunction
Aberrant mitochondrial dynamics disrupts mitochondrial function and contributes to disease conditions. A targeted RNA interference screen for deubiquitinating enzymes (DUBs) affecting protein levels of multifunctional mitochondrial fusion protein Mitofusin (MFN) identified USP8 prominently influenci...
Autores principales: | , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Life Science Alliance LLC
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6467245/ https://www.ncbi.nlm.nih.gov/pubmed/30988163 http://dx.doi.org/10.26508/lsa.201900392 |
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author | von Stockum, Sophia Sanchez-Martinez, Alvaro Corrà, Samantha Chakraborty, Joy Marchesan, Elena Locatello, Lisa Da Rè, Caterina Cusumano, Paola Caicci, Federico Ferrari, Vanni Costa, Rodolfo Bubacco, Luigi Rasotto, Maria Berica Szabo, Ildiko Whitworth, Alexander J Scorrano, Luca Ziviani, Elena |
author_facet | von Stockum, Sophia Sanchez-Martinez, Alvaro Corrà, Samantha Chakraborty, Joy Marchesan, Elena Locatello, Lisa Da Rè, Caterina Cusumano, Paola Caicci, Federico Ferrari, Vanni Costa, Rodolfo Bubacco, Luigi Rasotto, Maria Berica Szabo, Ildiko Whitworth, Alexander J Scorrano, Luca Ziviani, Elena |
author_sort | von Stockum, Sophia |
collection | PubMed |
description | Aberrant mitochondrial dynamics disrupts mitochondrial function and contributes to disease conditions. A targeted RNA interference screen for deubiquitinating enzymes (DUBs) affecting protein levels of multifunctional mitochondrial fusion protein Mitofusin (MFN) identified USP8 prominently influencing MFN levels. Genetic and pharmacological inhibition of USP8 normalized the elevated MFN protein levels observed in PINK1 and Parkin-deficient models. This correlated with improved mitochondrial function, locomotor performance and life span, and prevented dopaminergic neurons loss in Drosophila PINK1 KO flies. We identified a novel target antagonizing pathologically elevated MFN levels, mitochondrial dysfunction, and dopaminergic neuron loss of a Drosophila model of mitochondrial dysfunction. |
format | Online Article Text |
id | pubmed-6467245 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | Life Science Alliance LLC |
record_format | MEDLINE/PubMed |
spelling | pubmed-64672452019-04-17 Inhibition of the deubiquitinase USP8 corrects a Drosophila PINK1 model of mitochondria dysfunction von Stockum, Sophia Sanchez-Martinez, Alvaro Corrà, Samantha Chakraborty, Joy Marchesan, Elena Locatello, Lisa Da Rè, Caterina Cusumano, Paola Caicci, Federico Ferrari, Vanni Costa, Rodolfo Bubacco, Luigi Rasotto, Maria Berica Szabo, Ildiko Whitworth, Alexander J Scorrano, Luca Ziviani, Elena Life Sci Alliance Research Articles Aberrant mitochondrial dynamics disrupts mitochondrial function and contributes to disease conditions. A targeted RNA interference screen for deubiquitinating enzymes (DUBs) affecting protein levels of multifunctional mitochondrial fusion protein Mitofusin (MFN) identified USP8 prominently influencing MFN levels. Genetic and pharmacological inhibition of USP8 normalized the elevated MFN protein levels observed in PINK1 and Parkin-deficient models. This correlated with improved mitochondrial function, locomotor performance and life span, and prevented dopaminergic neurons loss in Drosophila PINK1 KO flies. We identified a novel target antagonizing pathologically elevated MFN levels, mitochondrial dysfunction, and dopaminergic neuron loss of a Drosophila model of mitochondrial dysfunction. Life Science Alliance LLC 2019-04-15 /pmc/articles/PMC6467245/ /pubmed/30988163 http://dx.doi.org/10.26508/lsa.201900392 Text en © 2019 von Stockum et al. 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 von Stockum, Sophia Sanchez-Martinez, Alvaro Corrà, Samantha Chakraborty, Joy Marchesan, Elena Locatello, Lisa Da Rè, Caterina Cusumano, Paola Caicci, Federico Ferrari, Vanni Costa, Rodolfo Bubacco, Luigi Rasotto, Maria Berica Szabo, Ildiko Whitworth, Alexander J Scorrano, Luca Ziviani, Elena Inhibition of the deubiquitinase USP8 corrects a Drosophila PINK1 model of mitochondria dysfunction |
title | Inhibition of the deubiquitinase USP8 corrects a Drosophila PINK1 model of mitochondria dysfunction |
title_full | Inhibition of the deubiquitinase USP8 corrects a Drosophila PINK1 model of mitochondria dysfunction |
title_fullStr | Inhibition of the deubiquitinase USP8 corrects a Drosophila PINK1 model of mitochondria dysfunction |
title_full_unstemmed | Inhibition of the deubiquitinase USP8 corrects a Drosophila PINK1 model of mitochondria dysfunction |
title_short | Inhibition of the deubiquitinase USP8 corrects a Drosophila PINK1 model of mitochondria dysfunction |
title_sort | inhibition of the deubiquitinase usp8 corrects a drosophila pink1 model of mitochondria dysfunction |
topic | Research Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6467245/ https://www.ncbi.nlm.nih.gov/pubmed/30988163 http://dx.doi.org/10.26508/lsa.201900392 |
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