TY - JOUR
T1 - COQ4 is required for the oxidative decarboxylation of the C1 carbon of coenzyme Q in eukaryotic cells
AU - Pelosi, Ludovic
AU - Morbiato, Laura
AU - Burgardt, Arthur
AU - Tonello, Fiorella
AU - Bartlett, Abigail K.
AU - Guerra, Rachel M.
AU - Ferizhendi, Katayoun Kazemzadeh
AU - Desbats, Maria Andrea
AU - Rascalou, Bérengère
AU - Marchi, Marco
AU - Vázquez-Fonseca, Luis
AU - Agosto, Caterina
AU - Zanotti, Giuseppe
AU - Roger-Margueritat, Morgane
AU - Alcázar-Fabra, María
AU - García-Corzo, Laura
AU - Sánchez-Cuesta, Ana
AU - Navas, Plácido
AU - Brea-Calvo, Gloria
AU - Trevisson, Eva
AU - Wendisch, Volker F.
AU - Pagliarini, David J.
AU - Salviati, Leonardo
AU - Pierrel, Fabien
N1 - Publisher Copyright:
© 2024 Elsevier Inc.
PY - 2024/3/7
Y1 - 2024/3/7
N2 - 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.
AB - 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.
KW - COQ4
KW - Corynebacterium
KW - coenzyme Q
KW - coenzyme Q biosynthesis
KW - coenzyme Q deficiency
KW - mitochondria
KW - oxidative decarboxylation
KW - respiratory chain
UR - http://www.scopus.com/inward/record.url?scp=85186283890&partnerID=8YFLogxK
U2 - 10.1016/j.molcel.2024.01.003
DO - 10.1016/j.molcel.2024.01.003
M3 - Article
C2 - 38295803
AN - SCOPUS:85186283890
SN - 1097-2765
VL - 84
SP - 981-989.e7
JO - Molecular cell
JF - Molecular cell
IS - 5
ER -