RT Journal Article
T1 Modelling the human coenzyme Q deficiency in Drosophila melanogaster
A1 Moreno Fernández-Ayala, Daniel José
A1 Jiménez Gancedo, S.
A1 Guerra, Ignacio
A1 Hernández Camacho, Juan Diego
A1 Neto, Marta
A1 Scialo, Filippo
A1 Astillero-López, Verónica
A1 Cortés Rodríguez, Ana Belén
A1 Santos-Ocaña, Carlos
A1 Rodríguez Aguilera, Juan Carlos
A1 Casares, Fernando
A1 Sanz, Alberto
A1 López-Lluch, Guillermo
A1 Navas, Plácido
K1 Coenzyme Q deficiency
K1 Drosophila melanogaster
K1 Animal model
AB The interference of the expression of each of the genes involved in the synthesis of coenzyme Q (CoQ) in Drosophila melanogaster can help to understand the pathophysiology of CoQ-dependent mitochondrial diseases in humans.We have knocked-down all genes involved in the CoQ biosynthesis pathway at different temperatures to induce depletion of CoQ at different levels throughout the body and in a tissue-specific manner. The efficiency of the knockdowns was quantified by Q-RTPCR and determination of CoQ levels by HPLC-UV + ECD. We performed mitochondria purification and quantified respiratory chain activity, both mitochondrial hydrogen peroxide and superoxide production, resistance to mechanical stress and determination of life expectancy. Finally, we evaluated the effect of CoQ10 supplementation as phenotype rescue therapy.D. melanogaster presents 3 isoforms of CoQ: CoQ8, CoQ9 and CoQ10. The level of depletion depended on the efficiency of the RNAi used and is specific for each gene. The interference of some genes interrupted fly development in embryogenesis (pdss2) or during metamorphosis (pdss1, coq3, coq5, coq8 and coq10), while in other cases viable adults can be obtained (coq2, coq6 and coq7). The knockdown of coq7 accumulated intermediates of the CoQ biosynthesis pathway at all stages of development, altered electron transfer with poor assembly of mitochondrial complexes, and deregulated mitochondrial hydrogen peroxide and superoxide production. Coq7 mutant flies showed partial lethality in metamorphosis, bang sensitivity and reduced life span of surviving animals. CoQ10 supplementation rescued the coq7-mutant phenotypes. Knock-down in the imaginal disc generated gene-specific eye deformities that can be mitigated by CoQ10 supplementation.Our results indicate that interference of the CoQ biosynthesis pathway in D. melanogaster shows a great diversity of phenotypes depending on the target gene, mirroring the heterogeneity of CoQ deficiency syndrome in humans and point to why mutations in certain genes are rarely found in patients.
PB Elsevier
YR 2025
FD 2025-01-27
LK https://hdl.handle.net/10433/24711
UL https://hdl.handle.net/10433/24711
LA en
NO Free Radical Biology and Medicine 230 (2025) 95–111
NO This research was funded by Instituto de Salud Carlos III (PI23/00815) to CS, PID2021-122671NB-I00 to FC, MCIN/AEI/10.13039/501100011033 (CEX2020-001088-M) to CABD.Funding for open access publishing: Universidad Pablo de Olavide/CBUA.Acknowledgement: We are highly grateful to 100%Natural (Madrid, Spain) for providing the soluble CoQ10 formulation.
NO Proyectos de investigaciónMCIN/AEI/10.13039/501100011033
NO Centro Andaluz de Biología del Desarrollo (CABD-CSIC/UPO)
NO Departamento de Fisiología, Anatomía y Biología Celular, Universidad Pablo de Olavide, Sevilla, Spain
NO CIBERER, U729, Instituto de Salud Carlos III, Madrid, Spain
NO School of Molecular Biosciences, College of Medical, Veterinary and Life Sciences, University of Glasgow, G12 8QQ, Glasgow, UK
DS RIO
RD May 22, 2026