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dc.contributor.authorLovero, Domenicaen
dc.contributor.authorGiordano, Lucaen
dc.contributor.authorMarsano, René Massimilianoen
dc.contributor.authorSanchez-Martinez, Alvaroen
dc.contributor.authorBoukhatmi, Hadien
dc.contributor.authorDrechsler, Maiken
dc.contributor.authorOliva, Martaen
dc.contributor.authorWhitworth, Alexen
dc.contributor.authorPorcelli, Damianoen
dc.contributor.authorCaggese, Corradoen
dc.date.accessioned2018-11-16T00:30:33Z
dc.date.available2018-11-16T00:30:33Z
dc.identifier.issn1932-6203
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/285123
dc.description.abstractMitochondrial 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.
dc.description.sponsorshipThis work was supported by grants from Ministero dell’Istruzione, dell’Università e della Ricerca (MIUR) to C.C. and University of Bari D.R. n. 12939 to D.P.
dc.languageengen
dc.publisherPLOS
dc.relation.isreplacedby1810/291111
dc.relation.isreplacedbyhttps://www.repository.cam.ac.uk/handle/1810/291111
dc.rightsAttribution 4.0 International
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/
dc.titleCharacterization of Drosophila ATPsynC mutants as a new model of mitochondrial ATP synthase disordersen
dc.typeArticle
prism.issueIdentifier8en
prism.numbere0201811en
prism.publicationNamePLoS Oneen
prism.volume13en
dc.identifier.doi10.17863/CAM.32494
dcterms.dateAccepted2018-07-23en
rioxxterms.versionofrecord10.1371/journal.pone.0201811en
rioxxterms.licenseref.urihttp://creativecommons.org/licenses/by/4.0/en
rioxxterms.licenseref.startdate2018-07-23en
dc.contributor.orcidWhitworth, Alex [0000-0002-1154-6629]
dc.identifier.eissn1932-6203
rioxxterms.typeJournal Article/Reviewen
pubs.funder-project-idMedical Research Council (MC_UU_00015/6)
cam.issuedOnline2018-08-10en


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Attribution 4.0 International
Except where otherwise noted, this item's licence is described as Attribution 4.0 International