Loss of Drosophila Coq8 results in impaired survival, locomotor deficits and photoreceptor degeneration

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dc.citation.issue1
dc.citation.volume15
dc.contributor.authorHura A
dc.contributor.authorHannah H
dc.contributor.authorTan WJ
dc.contributor.authorPenny R
dc.contributor.authorJessie J
dc.contributor.authorFitzsimons H
dc.date.available2022-02-09
dc.date.available2022-01-23
dc.date.issued9/02/2022
dc.description.abstractCoenzyme Q8A encodes the homologue of yeast coq8, an ATPase that is required for the biosynthesis of Coenzyme Q10, an essential component of the electron transport chain. Mutations in COQ8A in humans result in CoQ10 deficiency, the clinical features of which include early-onset cerebellar ataxia, seizures and intellectual disability. The rapid advancement of massively parallel sequencing has resulted in the identification of more than 40 new mutations in COQ8A and functional studies are required to confirm causality and to further research into determining the specific mechanisms through which the mutations result in loss of function. To that end, a Drosophila model of Coq8 deficiency was developed and characterized to determine its appropriateness as a model system to further explore the role of Coq8 in the brain, and for functional characterisation of Coq8 mutations. Pan-neuronal RNAi knockdown of Coq8 was largely lethal, with female escapers displaying severe locomotor deficits. Knockdown of Coq8 in the eye resulted in degeneration of photoreceptors, progressive necrosis and increased generation of reactive oxygen species. Reintroduction of wild-type Coq8 restored normal function, however expression of human wild-type COQ8A exacerbated the eye phenotype, suggesting it was acting as a dominant-negative. This model is therefore informative for investigating the function of Drosophila Coq8, however human COQ8A mutations cannot be assessed as hCOQ8A does not rescue Coq8 deficiency.
dc.description.publication-statusPublished
dc.identifierhttp://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000753395800001&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=c5bb3b2499afac691c2e3c1a83ef6fef
dc.identifierARTN 15
dc.identifier.citationMOLECULAR BRAIN, 2022, 15 (1)
dc.identifier.doi10.1186/s13041-022-00900-3
dc.identifier.eissn1756-6606
dc.identifier.elements-id451053
dc.identifier.harvestedMassey_Dark
dc.identifier.urihttps://hdl.handle.net/10179/16905
dc.publisherBioMed Central
dc.relation.isPartOfMOLECULAR BRAIN
dc.subjectcoq8
dc.subjectCOQ8A
dc.subjectCoenzyme Q10
dc.subjectBrain
dc.subjectNeuron
dc.subjectDrosophila
dc.subjectNeurodevelopment
dc.subjectNeurodegeneration
dc.subjectPhotoreceptor
dc.subjectMitochondria
dc.subject.anzsrc11 Medical and Health Sciences
dc.titleLoss of Drosophila Coq8 results in impaired survival, locomotor deficits and photoreceptor degeneration
dc.typeJournal article
pubs.notesNot known
pubs.organisational-group/Massey University
pubs.organisational-group/Massey University/College of Sciences
pubs.organisational-group/Massey University/College of Sciences/School of Natural Sciences
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