Functional characterization of human COQ4, a gene required for Coenzyme Q10 biosynthesis

Defects in genes involved in coenzyme Q (CoQ) biosynthesis cause primary CoQ deficiency, a severe multisystem disorders presenting as progressive encephalomyopathy and nephropathy. The CCQ4 gene encodes an essential factor for biosynthesis in Saccharomyces cerevisiae. We have identified and cloned i...

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Autores: Casarin A, Jimenez-Ortega JC, Trevisson E, Pertegato V, Doimo M, Ferrero-Gomez ML, Abbadi S, Artuch R, Quinzii C, Hirano M, Basso G, Ocaña CS, Navas P, Salviati L
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2008
País:España
Institución:Fundació Sant Joan de Déu
Repositorio:r-FSJD. Repositorio Institucional de Producción Científica de la Fundació Sant Joan de Déu
OAI Identifier:oai:fsjd.fundanetsuite.com:p1435
Acceso en línea:https://fsjd.fundanetsuite.com/Publicaciones/ProdCientif/PublicacionFrw.aspx?id=1435
Access Level:acceso abierto
Palabra clave:coenzyme Q(10)
coenzyme Q(10) deficiency
ubiquinone
biosynthesis
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spelling Functional characterization of human COQ4, a gene required for Coenzyme Q10 biosynthesisCasarin AJimenez-Ortega JCTrevisson EPertegato VDoimo MFerrero-Gomez MLAbbadi SArtuch RQuinzii CHirano MBasso GOcaña CSNavas PSalviati Lcoenzyme Q(10)coenzyme Q(10) deficiencyubiquinonebiosynthesisDefects in genes involved in coenzyme Q (CoQ) biosynthesis cause primary CoQ deficiency, a severe multisystem disorders presenting as progressive encephalomyopathy and nephropathy. The CCQ4 gene encodes an essential factor for biosynthesis in Saccharomyces cerevisiae. We have identified and cloned its human ortholog, COQ4, which is located on chromosome 9q34.13, and is transcribed into a 795 base-pair open reading frame, encoding a 265 amino acid (aa) protein (Isoform 1) with a predicted N-terminal mitochondrial targeting sequence. It shares 39% identity and 55% similarity with the yeast protein. Coq4 protein has no known enzymatic function, but may be a core component of multisub-unit complex required for CoQ biosynthesis. The human transcript is detected in Northern blots as a similar to 1.4 kb single band and is expressed ubiquitously, but at high levels in liver, lung, and pancreas. Transcription initiates at multiple sites, located 333-23 nucleotides upstream of the ATG. A second group of transcripts originating inside intron I of the gene encodes a 241 aa protein, which lacks the mitochondrial targeting sequence (isoform 2). Expression of GFP-fusion proteins in HeLa cells confirmed that only isoform 1 is targeted to mitochondria. The functional significance of the second isoform is unknown. Human COQ4 isoform 1, expressed from a multicopy plasmid, efficiently restores both growth in glycerol, and CoQ content in COQ4(null) yeast strains. Human CCQ4 is an interesting candidate gene for patients with isolated CoQ(10) deficiency. (C) 2008 Elsevier Inc. All rights reserved.ACADEMIC PRESS INC ELSEVIER SCIENCE2008info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttps://fsjd.fundanetsuite.com/Publicaciones/ProdCientif/PublicacionFrw.aspx?id=1435BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONSISSN: 0006291XISSNe: 10902104reponame:r-FSJD. Repositorio Institucional de Producción Científica de la Fundació Sant Joan de Déuinstname:Fundació Sant Joan de DéuInglésinfo:eu-repo/semantics/openAccessoai:fsjd.fundanetsuite.com:p14352026-05-27T12:37:41Z
dc.title.none.fl_str_mv Functional characterization of human COQ4, a gene required for Coenzyme Q10 biosynthesis
title Functional characterization of human COQ4, a gene required for Coenzyme Q10 biosynthesis
spellingShingle Functional characterization of human COQ4, a gene required for Coenzyme Q10 biosynthesis
Casarin A
coenzyme Q(10)
coenzyme Q(10) deficiency
ubiquinone
biosynthesis
title_short Functional characterization of human COQ4, a gene required for Coenzyme Q10 biosynthesis
title_full Functional characterization of human COQ4, a gene required for Coenzyme Q10 biosynthesis
title_fullStr Functional characterization of human COQ4, a gene required for Coenzyme Q10 biosynthesis
title_full_unstemmed Functional characterization of human COQ4, a gene required for Coenzyme Q10 biosynthesis
title_sort Functional characterization of human COQ4, a gene required for Coenzyme Q10 biosynthesis
dc.creator.none.fl_str_mv Casarin A
Jimenez-Ortega JC
Trevisson E
Pertegato V
Doimo M
Ferrero-Gomez ML
Abbadi S
Artuch R
Quinzii C
Hirano M
Basso G
Ocaña CS
Navas P
Salviati L
author Casarin A
author_facet Casarin A
Jimenez-Ortega JC
Trevisson E
Pertegato V
Doimo M
Ferrero-Gomez ML
Abbadi S
Artuch R
Quinzii C
Hirano M
Basso G
Ocaña CS
Navas P
Salviati L
author_role author
author2 Jimenez-Ortega JC
Trevisson E
Pertegato V
Doimo M
Ferrero-Gomez ML
Abbadi S
Artuch R
Quinzii C
Hirano M
Basso G
Ocaña CS
Navas P
Salviati L
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv coenzyme Q(10)
coenzyme Q(10) deficiency
ubiquinone
biosynthesis
topic coenzyme Q(10)
coenzyme Q(10) deficiency
ubiquinone
biosynthesis
description Defects in genes involved in coenzyme Q (CoQ) biosynthesis cause primary CoQ deficiency, a severe multisystem disorders presenting as progressive encephalomyopathy and nephropathy. The CCQ4 gene encodes an essential factor for biosynthesis in Saccharomyces cerevisiae. We have identified and cloned its human ortholog, COQ4, which is located on chromosome 9q34.13, and is transcribed into a 795 base-pair open reading frame, encoding a 265 amino acid (aa) protein (Isoform 1) with a predicted N-terminal mitochondrial targeting sequence. It shares 39% identity and 55% similarity with the yeast protein. Coq4 protein has no known enzymatic function, but may be a core component of multisub-unit complex required for CoQ biosynthesis. The human transcript is detected in Northern blots as a similar to 1.4 kb single band and is expressed ubiquitously, but at high levels in liver, lung, and pancreas. Transcription initiates at multiple sites, located 333-23 nucleotides upstream of the ATG. A second group of transcripts originating inside intron I of the gene encodes a 241 aa protein, which lacks the mitochondrial targeting sequence (isoform 2). Expression of GFP-fusion proteins in HeLa cells confirmed that only isoform 1 is targeted to mitochondria. The functional significance of the second isoform is unknown. Human COQ4 isoform 1, expressed from a multicopy plasmid, efficiently restores both growth in glycerol, and CoQ content in COQ4(null) yeast strains. Human CCQ4 is an interesting candidate gene for patients with isolated CoQ(10) deficiency. (C) 2008 Elsevier Inc. All rights reserved.
publishDate 2008
dc.date.none.fl_str_mv 2008
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv https://fsjd.fundanetsuite.com/Publicaciones/ProdCientif/PublicacionFrw.aspx?id=1435
url https://fsjd.fundanetsuite.com/Publicaciones/ProdCientif/PublicacionFrw.aspx?id=1435
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.publisher.none.fl_str_mv ACADEMIC PRESS INC ELSEVIER SCIENCE
publisher.none.fl_str_mv ACADEMIC PRESS INC ELSEVIER SCIENCE
dc.source.none.fl_str_mv BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
ISSN: 0006291X
ISSNe: 10902104
reponame:r-FSJD. Repositorio Institucional de Producción Científica de la Fundació Sant Joan de Déu
instname:Fundació Sant Joan de Déu
instname_str Fundació Sant Joan de Déu
reponame_str r-FSJD. Repositorio Institucional de Producción Científica de la Fundació Sant Joan de Déu
collection r-FSJD. Repositorio Institucional de Producción Científica de la Fundació Sant Joan de Déu
repository.name.fl_str_mv
repository.mail.fl_str_mv
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