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Updated: Jun 13, 2026
10:39
Visualization of ATP Synthase Dimers in Mitochondria by Electron Cryo-tomography
Published on: September 14, 2014
AP-3 and the V-ATPase modulate CTP synthase assembly through spatial association at the yeast vacuole
Michaela McCright1, Mitchell Leih1, Ayla Nack1
1Department of Molecular Cellular and Developmental Biology, University of Colorado, Boulder, CO 80309.
Molecular Biology of the Cell
|June 11, 2026
Summary
Metabolic enzyme filaments (cytoophidia) and vacuolar proton pumps (V-ATPases) are linked. AP-3 complex and V-ATPase inhibition impact cytoophidia assembly, revealing new cellular organization principles.
Area of Science:
- Cell Biology
- Biochemistry
- Molecular Biology
Background:
- Metabolic enzymes compartmentalize into cytoophidia, a conserved regulatory mechanism.
- Cytidine triphosphate synthase (CTPS) forms pH-sensitive cytoophidia.
- Nutritional deprivation affects CTPS cytoophidia and vacuolar H⁺-ATPase (V-ATPase) in yeast.
Purpose of the Study:
- To investigate the functional link between CTPS cytoophidia assembly and V-ATPase activity in yeast.
- To explore the role of the AP-3 adaptor complex in regulating CTPS cytoophidia.
Main Methods:
- Yeast genetics and microscopy.
- Analysis of protein localization and assembly dynamics.
- Pharmacological V-ATPase inhibition.
Main Results:
- Demonstrated spatial proximity between CTPS homologs (Ura7/Ura8), V-ATPase, and the AP-3 complex.
- Showed Ura7 localization to vacuoles under nutrient-rich and starvation conditions.
- Disruption of AP-3 altered Ura7 assembly dynamics, reducing structures but enhancing elongation.
- Combined V-ATPase inhibition and starvation induced massive Ura7 cytoophidia formation.
Conclusions:
- Revealed a spatial coupling between metabolic enzyme compartmentalization, vacuolar trafficking, and pH regulation.
- Suggested a novel organizational principle where CTPS assembly responds to vacuolar function.
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