Proteasome granule formation is regulated through mitochondrial respiration and kinase signaling.

In the yeast Saccharomyces cerevisiae, proteasomes are enriched in cell nuclei, in which they execute important cellular functions. Nutrient stress can change this localization, indicating that proteasomes respond to the metabolic state of the cell. However, the signals that connect these processes remain poorly understood. Carbon starvation triggers a reversible translocation of proteasomes to cytosolic condensates known as proteasome storage granules. Surprisingly, we observed strongly reduced levels of proteasome granules when cells had active cellular respiration prior to starvation. This suggests that the mitochondrial activity of cells is a determining factor in the response of proteasomes to carbon starvation. Consistent with this, upon inhibition of mitochondrial function, we observed that proteasomes relocalize to granules. These links between proteasomes and metabolism involve specific signaling pathways, as we identified a mitogen-activated protein kinase (MAPK) cascade that is critical to the formation of proteasome granules after respiratory growth but not following glycolytic growth. Furthermore, the yeast homolog of AMP kinase, Snf1, is important for proteasome granule formation induced by mitochondrial inhibitors, but it is dispensable for granule formation following carbon starvation. We propose a model in which mitochondrial activity promotes nuclear localization of the proteasome. This article has an associated First Person interview with the first author of the paper.