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Characterization of Drosophila ATPsynC mutants as a new model of mitochondrial ATP synthase disorders
Mitochondrial disorders associated with genetic defects of the ATP synthase are among the most deleterious diseases of the neuromuscular system that primarily manifest in newborns. Nevertheless, the number of established animal models for the elucidation of the molecular mechanisms behind such patho...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6086398/ https://www.ncbi.nlm.nih.gov/pubmed/30096161 http://dx.doi.org/10.1371/journal.pone.0201811 |
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author | Lovero, Domenica Giordano, Luca Marsano, René Massimiliano Sanchez-Martinez, Alvaro Boukhatmi, Hadi Drechsler, Maik Oliva, Marta Whitworth, Alexander J. Porcelli, Damiano Caggese, Corrado |
author_facet | Lovero, Domenica Giordano, Luca Marsano, René Massimiliano Sanchez-Martinez, Alvaro Boukhatmi, Hadi Drechsler, Maik Oliva, Marta Whitworth, Alexander J. Porcelli, Damiano Caggese, Corrado |
author_sort | Lovero, Domenica |
collection | PubMed |
description | Mitochondrial disorders associated with genetic defects of the ATP synthase are among the most deleterious diseases of the neuromuscular system that primarily manifest in newborns. Nevertheless, the number of established animal models for the elucidation of the molecular mechanisms behind such pathologies is limited. In this paper, we target the Drosophila melanogaster gene encoding for the ATP synthase subunit c, ATPsynC, in order to create a fruit fly model for investigating defects in mitochondrial bioenergetics and to better understand the comprehensive pathological spectrum associated with mitochondrial ATP synthase dysfunctions. Using P-element and EMS mutagenesis, we isolated a set of mutations showing a wide range of effects, from larval lethality to complex pleiotropic phenotypes encompassing developmental delay, early adult lethality, hypoactivity, sterility, hypofertility, aberrant male courtship behavior, locomotor defects and aberrant gonadogenesis. ATPsynC mutations impair ATP synthesis and mitochondrial morphology, and represent a powerful toolkit for the screening of genetic modifiers that can lead to potential therapeutic solutions. Furthermore, the molecular characterization of ATPsynC mutations allowed us to better understand the genetics of the ATPsynC locus and to define three broad pathological consequences of mutations affecting the mitochondrial ATP synthase functionality in Drosophila: i) pre-adult lethality; ii) multi-trait pathology accompanied by early adult lethality; iii) multi-trait adult pathology. We finally predict plausible parallelisms with genetic defects of mitochondrial ATP synthase in humans. |
format | Online Article Text |
id | pubmed-6086398 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-60863982018-08-28 Characterization of Drosophila ATPsynC mutants as a new model of mitochondrial ATP synthase disorders Lovero, Domenica Giordano, Luca Marsano, René Massimiliano Sanchez-Martinez, Alvaro Boukhatmi, Hadi Drechsler, Maik Oliva, Marta Whitworth, Alexander J. Porcelli, Damiano Caggese, Corrado PLoS One Research Article Mitochondrial disorders associated with genetic defects of the ATP synthase are among the most deleterious diseases of the neuromuscular system that primarily manifest in newborns. Nevertheless, the number of established animal models for the elucidation of the molecular mechanisms behind such pathologies is limited. In this paper, we target the Drosophila melanogaster gene encoding for the ATP synthase subunit c, ATPsynC, in order to create a fruit fly model for investigating defects in mitochondrial bioenergetics and to better understand the comprehensive pathological spectrum associated with mitochondrial ATP synthase dysfunctions. Using P-element and EMS mutagenesis, we isolated a set of mutations showing a wide range of effects, from larval lethality to complex pleiotropic phenotypes encompassing developmental delay, early adult lethality, hypoactivity, sterility, hypofertility, aberrant male courtship behavior, locomotor defects and aberrant gonadogenesis. ATPsynC mutations impair ATP synthesis and mitochondrial morphology, and represent a powerful toolkit for the screening of genetic modifiers that can lead to potential therapeutic solutions. Furthermore, the molecular characterization of ATPsynC mutations allowed us to better understand the genetics of the ATPsynC locus and to define three broad pathological consequences of mutations affecting the mitochondrial ATP synthase functionality in Drosophila: i) pre-adult lethality; ii) multi-trait pathology accompanied by early adult lethality; iii) multi-trait adult pathology. We finally predict plausible parallelisms with genetic defects of mitochondrial ATP synthase in humans. Public Library of Science 2018-08-10 /pmc/articles/PMC6086398/ /pubmed/30096161 http://dx.doi.org/10.1371/journal.pone.0201811 Text en © 2018 Lovero et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Research Article Lovero, Domenica Giordano, Luca Marsano, René Massimiliano Sanchez-Martinez, Alvaro Boukhatmi, Hadi Drechsler, Maik Oliva, Marta Whitworth, Alexander J. Porcelli, Damiano Caggese, Corrado Characterization of Drosophila ATPsynC mutants as a new model of mitochondrial ATP synthase disorders |
title | Characterization of Drosophila ATPsynC mutants as a new model of mitochondrial ATP synthase disorders |
title_full | Characterization of Drosophila ATPsynC mutants as a new model of mitochondrial ATP synthase disorders |
title_fullStr | Characterization of Drosophila ATPsynC mutants as a new model of mitochondrial ATP synthase disorders |
title_full_unstemmed | Characterization of Drosophila ATPsynC mutants as a new model of mitochondrial ATP synthase disorders |
title_short | Characterization of Drosophila ATPsynC mutants as a new model of mitochondrial ATP synthase disorders |
title_sort | characterization of drosophila atpsync mutants as a new model of mitochondrial atp synthase disorders |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6086398/ https://www.ncbi.nlm.nih.gov/pubmed/30096161 http://dx.doi.org/10.1371/journal.pone.0201811 |
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