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...

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Detalles Bibliográficos
Autores: 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
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
Descripción
Sumario: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.

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