# Acetic acid induces proteasome storage granule formation and inhibits proteasomal proteolysis: Comparison with other induction conditions

## TL;DR

Acetic acid causes yeast cells to form proteasome storage granules more quickly than other conditions, offering new insights into how these granules form.

## Contribution

The study identifies acetic acid as a new inducer of proteasome storage granules and reveals condition-specific mechanisms.

## Key findings

- Acetic acid induces PSG formation faster than glucose depletion or mitochondrial stress.
- Acetic acid inhibits proteasomal proteolysis, leading to ubiquitinated protein accumulation.
- Key factors like Sem1/Dss1 and Rpn10/Rpn13 vary in importance depending on the induction condition.

## Abstract

Proteasomes are primarily located within the nuclei of proliferating cells; however, their localization changes dynamically in response to environmental conditions. Saccharomyces cerevisiae forms proteasome storage granules (PSGs) in the cytoplasm upon glucose depletion, mitochondrial stress, or transition to quiescence. Although intracellular acidification drives PSG formation, the detailed mechanisms underlying this process are unclear. As the established PSG induction conditions are limited to the three conditions mentioned above, identifying other induction conditions will elucidate these mechanisms. The current study showed that acetic acid stress induced PSG formation more rapidly than other PSG induction conditions following the formation of nuclear proteasome condensates. Acetic acid inhibited proteasomal proteolysis, leading to the accumulation of ubiquitinated proteins. Of the non-essential proteasome subunits, Sem1/Dss1 was crucial, but Pre9 was less important for PSG formation under all conditions. The necessity of Rpn10 and Rpn13 for PSG formation differed depending on induction conditions. The proteasome shuttle factors, Dsk2 and Rad23, colocalized with all PSGs but were not essential for PSG formation caused by acetic acid or glucose depletion. The contributions of Hul5, an E3 ubiquitin ligase, and new protein synthesis to PSG formation also differed among the conditions, indicating that the key factors for PSG formation varied among the different induction conditions. These findings provide novel insights into the physiological effects of acetic acid on proteasomes and PSG-formation mechanisms.