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Updated: Aug 5, 2026
05:27
Inner Mitochondrial Membrane Sensitivity to Na+ Reveals Partially Segmented Functional CoQ Pools
Published on: July 20, 2022
COQ8 chaperones coenzyme Q lipid intermediates through ATP-driven structural gating
Andrea Gottinger1, Marco Malatesta1, Callum R Nicoll1
1Department of Biology and Biotechnology 'Lazzaro Spallanzani', University of Pavia, Via Ferrata 9, 27100 Pavia, Italy.
Science Advances
|July 29, 2026
Summary
COQ8 proteins are ATPases that help synthesize Coenzyme Q. They bind intermediates and are regulated by the final product, revealing a new feedback mechanism for Coenzyme Q biosynthesis.
Area of Science:
- Biochemistry
- Molecular Biology
- Structural Biology
Background:
- Coenzyme Q biosynthesis involves atypical kinase-like proteins COQ8A and COQ8B.
- The precise molecular mechanism of COQ8 proteins is not fully understood.
Purpose of the Study:
- To elucidate the molecular mechanism of COQ8A and COQ8B in Coenzyme Q biosynthesis.
- To investigate how COQ8 proteins interact with biosynthetic intermediates and regulate the process.
Main Methods:
- Biochemical assays to determine ATPase activity.
- Structural bioinformatics and mutagenesis to identify functional sites.
- X-ray crystallography to resolve protein-ligand interactions.
- Analysis of pathological variants.
Main Results:
- COQ8 proteins function as ATPases, promoting Coenzyme Q biosynthetic metabolon activity.
- They engage in protein-protein interactions and chaperone insoluble intermediates.
- A novel pocket recognizes Coenzyme Q intermediates via head group interactions.
- ATP hydrolysis gates access to this pocket through conformational changes.
- Excess Coenzyme Q inhibits COQ8's promoting effect by preventing intermediate binding.
Conclusions:
- COQ8 proteins act as ATPases that chaperone Coenzyme Q biosynthetic intermediates.
- A feedback inhibition mechanism, regulated by excess Coenzyme Q, tunes the biosynthesis pathway.
- These findings provide a model for COQ8-mediated regulation of Coenzyme Q production.
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