COQ4 is required for the oxidative decarboxylation of the C1 carbon of coenzyme Q in eukaryotic cells
Coenzyme Q (CoQ) is a redox lipid that fulfills critical functions in cellular bioenergetics and homeostasis. CoQ is synthesized by a multi-step pathway that involves several COQ proteins. Two steps of the eukaryotic pathway, the decarboxylation and hydroxylation of position C1, have remained unchar...
| Autores: | , , , , , , , , , , , , , , , , , , , , , , , |
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| Tipo de recurso: | artículo |
| Estado: | Versión aceptada para publicación |
| Fecha de publicación: | 2024 |
| País: | España |
| Institución: | Consejo Superior de Investigaciones Científicas (CSIC) |
| Repositorio: | DIGITAL.CSIC. Repositorio Institucional del CSIC |
| OAI Identifier: | oai:digital.csic.es:10261/365193 |
| Acceso en línea: | http://hdl.handle.net/10261/365193 |
| Access Level: | acceso abierto |
| Palabra clave: | Coenzyme Q Coenzyme Q biosynthesis COQ4 Oxidative decarboxylation Mitochondria Respiratory chain Coenzyme Q deficiency Corynebacterium |
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COQ4 is required for the oxidative decarboxylation of the C1 carbon of coenzyme Q in eukaryotic cellsPelosi, LudovicMorbiato, LauraBurgardt, ArthurTonello, FiorellaBartlett, Abigail K.Guerra, Rachel M.Ferizhendi, Katayoun KazemzadehDesbats, María AndreaRascalou, BérengèreMarchi, MarcoVázquez-Fonseca, LuisAgosto, CaterinaZanotti, GiuseppeRoger-Margueritat, MorganeAlcázar-Fabra, MaríaGarcía-Corzo, LauraSánchez-Cuesta, AnaNavas, PlácidoBrea-Calvo, GloriaTrevisson, EvaWendisch, Volker F.Pagliarini, David J.Salviati, LeonardoPierrel, FabienCoenzyme QCoenzyme Q biosynthesisCOQ4Oxidative decarboxylationMitochondriaRespiratory chainCoenzyme Q deficiencyCorynebacteriumCoenzyme Q (CoQ) is a redox lipid that fulfills critical functions in cellular bioenergetics and homeostasis. CoQ is synthesized by a multi-step pathway that involves several COQ proteins. Two steps of the eukaryotic pathway, the decarboxylation and hydroxylation of position C1, have remained uncharacterized. Here, we provide evidence that these two reactions occur in a single oxidative decarboxylation step catalyzed by COQ4. We demonstrate that COQ4 complements an Escherichia coli strain deficient for C1 decarboxylation and hydroxylation and that COQ4 displays oxidative decarboxylation activity in the non-CoQ producer Corynebacterium glutamicum. Overall, our results substantiate that COQ4 contributes to CoQ biosynthesis, not only via its previously proposed structural role but also via the oxidative decarboxylation of CoQ precursors. These findings fill a major gap in the knowledge of eukaryotic CoQ biosynthesis and shed light on the pathophysiology of human primary CoQ deficiency due to COQ4 mutations.This work was supported by grants from the ANR to F.P. (ANR-19-CE44-0014O2-TABOO), from the NIH to D.J.P. (R35GM131795), from Telethon Italy (GGP13222 and 14187c), from Fondazione IRP Città della Speranza (to L.S.), from Fondazione CARIPARO (2019 FCR) to E.T., and from European Regional Development Fund (FEDER)/Andalusian Regional Government, Spain (FEDER operational program 2014–2020; P18-RT-4572) to G.B.-C. and P.N.Peer reviewedCell PressAgence Nationale de la Recherche (France)National Institutes of Health (US)Telethon ItaliaFondazione CariparoEuropean CommissionJunta de AndalucíaConsejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]202420242024info:eu-repo/semantics/articlehttp://purl.org/coar/resource_type/c_6501Postprintinfo:eu-repo/semantics/acceptedVersionapplication/pdfhttp://hdl.handle.net/10261/365193reponame:DIGITAL.CSIC. Repositorio Institucional del CSICinstname:Consejo Superior de Investigaciones Científicas (CSIC)InglésThe underlying dataset has been published as supplementary material of the article in the publisher platform at DOI https://doi.org/10.1016/j.molcel.2024.01.003https://doi.org/10.1016/j.molcel.2024.01.003Síinfo:eu-repo/semantics/openAccessoai:digital.csic.es:10261/3651932026-05-22T06:33:51Z |
| dc.title.none.fl_str_mv |
COQ4 is required for the oxidative decarboxylation of the C1 carbon of coenzyme Q in eukaryotic cells |
| title |
COQ4 is required for the oxidative decarboxylation of the C1 carbon of coenzyme Q in eukaryotic cells |
| spellingShingle |
COQ4 is required for the oxidative decarboxylation of the C1 carbon of coenzyme Q in eukaryotic cells Pelosi, Ludovic Coenzyme Q Coenzyme Q biosynthesis COQ4 Oxidative decarboxylation Mitochondria Respiratory chain Coenzyme Q deficiency Corynebacterium |
| title_short |
COQ4 is required for the oxidative decarboxylation of the C1 carbon of coenzyme Q in eukaryotic cells |
| title_full |
COQ4 is required for the oxidative decarboxylation of the C1 carbon of coenzyme Q in eukaryotic cells |
| title_fullStr |
COQ4 is required for the oxidative decarboxylation of the C1 carbon of coenzyme Q in eukaryotic cells |
| title_full_unstemmed |
COQ4 is required for the oxidative decarboxylation of the C1 carbon of coenzyme Q in eukaryotic cells |
| title_sort |
COQ4 is required for the oxidative decarboxylation of the C1 carbon of coenzyme Q in eukaryotic cells |
| dc.creator.none.fl_str_mv |
Pelosi, Ludovic Morbiato, Laura Burgardt, Arthur Tonello, Fiorella Bartlett, Abigail K. Guerra, Rachel M. Ferizhendi, Katayoun Kazemzadeh Desbats, María Andrea Rascalou, Bérengère Marchi, Marco Vázquez-Fonseca, Luis Agosto, Caterina Zanotti, Giuseppe Roger-Margueritat, Morgane Alcázar-Fabra, María García-Corzo, Laura Sánchez-Cuesta, Ana Navas, Plácido Brea-Calvo, Gloria Trevisson, Eva Wendisch, Volker F. Pagliarini, David J. Salviati, Leonardo Pierrel, Fabien |
| author |
Pelosi, Ludovic |
| author_facet |
Pelosi, Ludovic Morbiato, Laura Burgardt, Arthur Tonello, Fiorella Bartlett, Abigail K. Guerra, Rachel M. Ferizhendi, Katayoun Kazemzadeh Desbats, María Andrea Rascalou, Bérengère Marchi, Marco Vázquez-Fonseca, Luis Agosto, Caterina Zanotti, Giuseppe Roger-Margueritat, Morgane Alcázar-Fabra, María García-Corzo, Laura Sánchez-Cuesta, Ana Navas, Plácido Brea-Calvo, Gloria Trevisson, Eva Wendisch, Volker F. Pagliarini, David J. Salviati, Leonardo Pierrel, Fabien |
| author_role |
author |
| author2 |
Morbiato, Laura Burgardt, Arthur Tonello, Fiorella Bartlett, Abigail K. Guerra, Rachel M. Ferizhendi, Katayoun Kazemzadeh Desbats, María Andrea Rascalou, Bérengère Marchi, Marco Vázquez-Fonseca, Luis Agosto, Caterina Zanotti, Giuseppe Roger-Margueritat, Morgane Alcázar-Fabra, María García-Corzo, Laura Sánchez-Cuesta, Ana Navas, Plácido Brea-Calvo, Gloria Trevisson, Eva Wendisch, Volker F. Pagliarini, David J. Salviati, Leonardo Pierrel, Fabien |
| author2_role |
author author author author author author author author author author author author author author author author author author author author author author author |
| dc.contributor.none.fl_str_mv |
Agence Nationale de la Recherche (France) National Institutes of Health (US) Telethon Italia Fondazione Cariparo European Commission Junta de Andalucía Consejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72] |
| dc.subject.none.fl_str_mv |
Coenzyme Q Coenzyme Q biosynthesis COQ4 Oxidative decarboxylation Mitochondria Respiratory chain Coenzyme Q deficiency Corynebacterium |
| topic |
Coenzyme Q Coenzyme Q biosynthesis COQ4 Oxidative decarboxylation Mitochondria Respiratory chain Coenzyme Q deficiency Corynebacterium |
| description |
Coenzyme Q (CoQ) is a redox lipid that fulfills critical functions in cellular bioenergetics and homeostasis. CoQ is synthesized by a multi-step pathway that involves several COQ proteins. Two steps of the eukaryotic pathway, the decarboxylation and hydroxylation of position C1, have remained uncharacterized. Here, we provide evidence that these two reactions occur in a single oxidative decarboxylation step catalyzed by COQ4. We demonstrate that COQ4 complements an Escherichia coli strain deficient for C1 decarboxylation and hydroxylation and that COQ4 displays oxidative decarboxylation activity in the non-CoQ producer Corynebacterium glutamicum. Overall, our results substantiate that COQ4 contributes to CoQ biosynthesis, not only via its previously proposed structural role but also via the oxidative decarboxylation of CoQ precursors. These findings fill a major gap in the knowledge of eukaryotic CoQ biosynthesis and shed light on the pathophysiology of human primary CoQ deficiency due to COQ4 mutations. |
| publishDate |
2024 |
| dc.date.none.fl_str_mv |
2024 2024 2024 |
| dc.type.none.fl_str_mv |
info:eu-repo/semantics/article http://purl.org/coar/resource_type/c_6501 Postprint info:eu-repo/semantics/acceptedVersion |
| format |
article |
| status_str |
acceptedVersion |
| dc.identifier.none.fl_str_mv |
http://hdl.handle.net/10261/365193 |
| url |
http://hdl.handle.net/10261/365193 |
| dc.language.none.fl_str_mv |
Inglés |
| language_invalid_str_mv |
Inglés |
| dc.relation.none.fl_str_mv |
The underlying dataset has been published as supplementary material of the article in the publisher platform at DOI https://doi.org/10.1016/j.molcel.2024.01.003 https://doi.org/10.1016/j.molcel.2024.01.003 Sí |
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info:eu-repo/semantics/openAccess |
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openAccess |
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application/pdf |
| dc.publisher.none.fl_str_mv |
Cell Press |
| publisher.none.fl_str_mv |
Cell Press |
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reponame:DIGITAL.CSIC. Repositorio Institucional del CSIC instname:Consejo Superior de Investigaciones Científicas (CSIC) |
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Consejo Superior de Investigaciones Científicas (CSIC) |
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DIGITAL.CSIC. Repositorio Institucional del CSIC |
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DIGITAL.CSIC. Repositorio Institucional del CSIC |
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