eprintid: 1568103
rev_number: 25
eprint_status: archive
userid: 608
dir: disk0/01/56/81/03
datestamp: 2017-08-03 15:03:18
lastmod: 2021-12-10 23:53:58
status_changed: 2017-08-03 15:03:18
type: article
metadata_visibility: show
creators_name: He, CH
creators_name: Black, DS
creators_name: Allan, CM
creators_name: Meunier, B
creators_name: Rahman, S
creators_name: Clarke, CF
title: Human COQ9 Rescues a coq9 Yeast Mutant by Enhancing Coenzyme Q Biosynthesis from 4-Hydroxybenzoic Acid and Stabilizing the CoQ-Synthome
ispublished: pub
divisions: UCL
divisions: B02
divisions: D13
divisions: G23
keywords: Science & Technology, Life Sciences & Biomedicine, Physiology, Human Homolog, Temperature-Sensitive Mutant, Coenzyme Q, Immunoprecipitation, Saccharomyces Cerevisiae, Mitochondrial Metabolism, Para-Aminobenzoic Acid, Saccharomyces-Cerevisiae, Ubiquinone Biosynthesis, C-Methyltransferase, Genetic-Evidence, Null Mutants, Protein, Polypeptide, Deficiency, Encodes
note: © 2017 He, Black, Allan, Meunier, Rahman and Clarke. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
abstract: Coq9 is required for the stability of a mitochondrial multi-subunit complex, termed the CoQ-synthome, and the deamination step of Q intermediates that derive from para-aminobenzoic acid (pABA) in yeast. In human, mutations in the COQ9 gene cause neonatal-onset primary Q10 deficiency. In this study, we determined whether expression of human COQ9 could complement yeast coq9 point or null mutants. We found that expression of human COQ9 rescues the growth of the temperature-sensitive yeast mutant, coq9-ts19, on a non-fermentable carbon source and increases the content of Q6, by enhancing Q biosynthesis from 4-hydroxybenzoic acid (4HB). To study the mechanism for the rescue by human COQ9, we determined the steady-state levels of yeast Coq polypeptides in the mitochondria of the temperature-sensitive yeast coq9 mutant expressing human COQ9. We show that the expression of human COQ9 significantly increased steady-state levels of yeast Coq4, Coq6, Coq7, and Coq9 at permissive temperature. Human COQ9 polypeptide levels persisted at non-permissive temperature. A small amount of the human COQ9 co-purified with tagged Coq6, Coq6-CNAP, indicating that human COQ9 interacts with the yeast Q-biosynthetic complex. These findings suggest that human COQ9 rescues the yeast coq9 temperature-sensitive mutant by stabilizing the CoQ-synthome and increasing Q biosynthesis from 4HB. This finding provides a powerful approach to studying the function of human COQ9 using yeast as a model.
date: 2017-07-07
date_type: published
publisher: FRONTIERS MEDIA SA
official_url: https://doi.org/10.3389/fphys.2017.00463
oa_status: green
full_text_type: pub
language: eng
primo: open
primo_central: open_green
article_type_text: Article
verified: verified_manual
elements_id: 1406961
doi: 10.3389/fphys.2017.00463
language_elements: English
lyricists_name: Rahman, Shamima
lyricists_id: SRAHM75
actors_name: Bracey, Alan
actors_id: ABBRA90
actors_role: owner
full_text_status: public
publication: Frontiers in Physiology
volume: 8
article_number: 463
pages: 10
issn: 1664-042X
citation:        He, CH;    Black, DS;    Allan, CM;    Meunier, B;    Rahman, S;    Clarke, CF;      (2017)    Human COQ9 Rescues a coq9 Yeast Mutant by Enhancing Coenzyme Q Biosynthesis from 4-Hydroxybenzoic Acid and Stabilizing the CoQ-Synthome.                   Frontiers in Physiology , 8     , Article 463.  10.3389/fphys.2017.00463 <https://doi.org/10.3389/fphys.2017.00463>.       Green open access   
 
document_url: https://discovery.ucl.ac.uk/id/eprint/1568103/1/fphys-08-00463.pdf