To save or degrade: balancing proteasome homeostasis to maximize cell survival

ABSTRACT

Autophagic degradation of proteasomes (termed proteaphagy) is a conserved mechanism by which cells eliminate excess or damaged particles. This clearance is induced rapidly when organisms are starved for nitrogen and, because proteasomes are highly abundant, their breakdown likely makes an important contribution to the amino acid pools necessary for survival. By contrast, our recent studies found that proteasomes are not degraded in response to carbon starvation, even though bulk macroautophagy is similarly activated. Instead, carbon starvation induces sequestration of proteasomes into membrane-less cytoplasmic condensates previously termed proteasome storage granules (PSGs), which protect proteasomes from autophagic degradation. Preserving proteasomes in PSGs enhances the ability of yeast cells to recover from a variety of stresses, implying that rapid remobilization of stored proteasomes when conditions improve is advantageous to cell fitness. Consequently, the choice of whether to save or degrade proteasomes can profoundly impact cell survival.

KEYWORDS:

• ATP
• Blm10
• carbon starvation
• pH
• proteaphagy
• proteasome
• proteasome storage granules
• Spg5
• ubiquitin
• Ubp3

Acknowledgments

The authors wish to thank Robert C. Augustine for critical reading of the manuscript.

Disclosure statement

No potential conflict of interest was reported by the authors.

Additional information

Funding

This work was funded by grants from the U.S. Department of Energy Office of Science; Office of Basic Energy Science; Chemical Sciences, Geosciences and Biosciences Division (DE-FG02-88ER13968); the National Science Foundation; Plant Genome Research Program (IOS-1329956); and the National Institutes of Health; National Institute of General Medical Science (R01-GM124452-01A1).