Developmental arrest in Drosophila melanogaster caused by mitochondrial DNA replication defects cannot be rescued by the alternative oxidase

Abstract The xenotopic expression of the alternative oxidase AOX from the tunicate Ciona intestinalis in diverse models of human disease partially alleviates the phenotypic effects of mitochondrial respiratory chain defects. AOX is a non-proton pumping, mitochondrial inner membrane-bound, single-sub...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Ana Paula C. Rodrigues, André F. Camargo, Ana Andjelković, Howard T. Jacobs, Marcos T. Oliveira
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2018
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/8d4f904e88654e5884d32d4206b5cd34
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:8d4f904e88654e5884d32d4206b5cd34
record_format	dspace
spelling	oai:doaj.org-article:8d4f904e88654e5884d32d4206b5cd342021-12-02T15:08:12ZDevelopmental arrest in Drosophila melanogaster caused by mitochondrial DNA replication defects cannot be rescued by the alternative oxidase10.1038/s41598-018-29150-x2045-2322https://doaj.org/article/8d4f904e88654e5884d32d4206b5cd342018-07-01T00:00:00Zhttps://doi.org/10.1038/s41598-018-29150-xhttps://doaj.org/toc/2045-2322Abstract The xenotopic expression of the alternative oxidase AOX from the tunicate Ciona intestinalis in diverse models of human disease partially alleviates the phenotypic effects of mitochondrial respiratory chain defects. AOX is a non-proton pumping, mitochondrial inner membrane-bound, single-subunit enzyme that can bypass electron transport through the cytochrome segment, providing an additional site for ubiquinone reoxidation and oxygen reduction upon respiratory chain overload. We set out to investigate whether AOX expression in Drosophila could counteract the effects of mitochondrial DNA (mtDNA) replication defects caused by disturbances in the mtDNA helicase or DNA polymerase γ. We observed that the developmental arrest imposed by either the expression of mutant forms of these enzymes or their knockdown was not rescued by AOX. Considering also the inability of AOX to ameliorate the phenotype of tko 25t , a fly mutant with mitochondrial translation deficiency, we infer that this alternative enzyme may not be applicable to cases of mitochondrial gene expression defects. Finding the limitations of AOX applicability will help establish the parameters for the future putative use of this enzyme in gene therapies for human mitochondrial diseases.Ana Paula C. RodriguesAndré F. CamargoAna AndjelkovićHoward T. JacobsMarcos T. OliveiraNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 8, Iss 1, Pp 1-10 (2018)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Ana Paula C. Rodrigues André F. Camargo Ana Andjelković Howard T. Jacobs Marcos T. Oliveira Developmental arrest in Drosophila melanogaster caused by mitochondrial DNA replication defects cannot be rescued by the alternative oxidase
description	Abstract The xenotopic expression of the alternative oxidase AOX from the tunicate Ciona intestinalis in diverse models of human disease partially alleviates the phenotypic effects of mitochondrial respiratory chain defects. AOX is a non-proton pumping, mitochondrial inner membrane-bound, single-subunit enzyme that can bypass electron transport through the cytochrome segment, providing an additional site for ubiquinone reoxidation and oxygen reduction upon respiratory chain overload. We set out to investigate whether AOX expression in Drosophila could counteract the effects of mitochondrial DNA (mtDNA) replication defects caused by disturbances in the mtDNA helicase or DNA polymerase γ. We observed that the developmental arrest imposed by either the expression of mutant forms of these enzymes or their knockdown was not rescued by AOX. Considering also the inability of AOX to ameliorate the phenotype of tko 25t , a fly mutant with mitochondrial translation deficiency, we infer that this alternative enzyme may not be applicable to cases of mitochondrial gene expression defects. Finding the limitations of AOX applicability will help establish the parameters for the future putative use of this enzyme in gene therapies for human mitochondrial diseases.
format	article
author	Ana Paula C. Rodrigues André F. Camargo Ana Andjelković Howard T. Jacobs Marcos T. Oliveira
author_facet	Ana Paula C. Rodrigues André F. Camargo Ana Andjelković Howard T. Jacobs Marcos T. Oliveira
author_sort	Ana Paula C. Rodrigues
title	Developmental arrest in Drosophila melanogaster caused by mitochondrial DNA replication defects cannot be rescued by the alternative oxidase
title_short	Developmental arrest in Drosophila melanogaster caused by mitochondrial DNA replication defects cannot be rescued by the alternative oxidase
title_full	Developmental arrest in Drosophila melanogaster caused by mitochondrial DNA replication defects cannot be rescued by the alternative oxidase
title_fullStr	Developmental arrest in Drosophila melanogaster caused by mitochondrial DNA replication defects cannot be rescued by the alternative oxidase
title_full_unstemmed	Developmental arrest in Drosophila melanogaster caused by mitochondrial DNA replication defects cannot be rescued by the alternative oxidase
title_sort	developmental arrest in drosophila melanogaster caused by mitochondrial dna replication defects cannot be rescued by the alternative oxidase
publisher	Nature Portfolio
publishDate	2018
url	https://doaj.org/article/8d4f904e88654e5884d32d4206b5cd34
work_keys_str_mv	AT anapaulacrodrigues developmentalarrestindrosophilamelanogastercausedbymitochondrialdnareplicationdefectscannotberescuedbythealternativeoxidase AT andrefcamargo developmentalarrestindrosophilamelanogastercausedbymitochondrialdnareplicationdefectscannotberescuedbythealternativeoxidase AT anaandjelkovic developmentalarrestindrosophilamelanogastercausedbymitochondrialdnareplicationdefectscannotberescuedbythealternativeoxidase AT howardtjacobs developmentalarrestindrosophilamelanogastercausedbymitochondrialdnareplicationdefectscannotberescuedbythealternativeoxidase AT marcostoliveira developmentalarrestindrosophilamelanogastercausedbymitochondrialdnareplicationdefectscannotberescuedbythealternativeoxidase
_version_	1718388262593101824

Developmental arrest in Drosophila melanogaster caused by mitochondrial DNA replication defects cannot be rescued by the alternative oxidase

Ejemplares similares