COQ8 chaperones coenzyme Q lipid intermediates through ATP-driven structural gating.

Authors

Andrea Gottinger, Marco Malatesta, Callum R Nicoll, Georg Ansari, Mathieu Quinodoz, Karolina Kaminska, Rachael W C Tang, Tien-En Tan, Beau J Fenner, Pilar Barberán-Martínez, Gema García-García, José M Millán, Maximilian Pfau, Natalie E Burbach, Domiziana Cecchini, Carlo Rivolta, Andrea Mattevi

Published in

Science advances. Volume 12. Issue 31. Pages eaeg1124. Jul 31, 2026. Epub Jul 29, 2026.

Abstract

Coenzyme Q biosynthesis requires two atypical kinase-like proteins (COQ8A and COQ8B), whose detailed molecular mechanism remains unclear. Here, we show that both paralogs function as adenosine triphosphatases (ATPases) that promote coenzyme Q biosynthetic metabolon activity by engaging in loose protein-protein interactions and delivering insoluble biosynthetic intermediates. Structural bioinformatics and pathological variant-driven mutagenesis identify a previously uncharacterized pocket that selectively recognizes coenzyme Q biosynthetic intermediates via their head groups. X-ray crystallography reveals that access to this pocket is gated by long-range conformational changes controlled by adenosine 5'-triphosphate hydrolysis. Last, excess coenzyme Q suppresses binding of early-stage intermediates and thereby abolishes the promoting effect of COQ8 on the metabolon. Together, these findings support a model in which COQ8 tunes coenzyme Q biosynthesis by coupling ATPase-driven intermediate chaperoning to feedback inhibition by the final product.

PMID:
42525751
Bibliographic data and abstract were imported from PubMed on 30 Jul 2026.

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