RETRACTED: Proteasome storage granules protect proteasomes from autophagic degradation upon carbon starvation

Abstract

26S proteasome abundance is tightly regulated at multiple levels, including the elimination of excess or inactive particles by autophagy. In yeast, this proteaphagy occurs upon nitrogen starvation but not carbon starvation, which instead stimulates the rapid sequestration of proteasomes into cytoplasmic puncta termed proteasome storage granules (PSGs). Here, we show that PSGs help protect proteasomes from autophagic degradation. Both the core protease and regulatory particle sub-complexes are sequestered separately into PSGs via pathways dependent on the accessory proteins Blm10 and Spg5, respectively. Modulating PSG formation, either by perturbing cellular energy status or pH, or by genetically eliminating factors required for granule assembly, not only influences the rate of proteasome degradation, but also impacts cell viability upon recovery from carbon starvation. PSG formation and concomitant protection against proteaphagy also occurs in Arabidopsis, suggesting that PSGs represent an evolutionarily conserved cache of proteasomes that can be rapidly re-mobilized based on energy availability.

Proteasome 19S RP and translation preinitiation complexes are secreted within exosomes upon serum starvation

“…Starvation, like oxidative stress, is known to induce disassembly of the 26S proteasome into its 19S and 20S particles in yeast cells . Both 20S CP and 19S RP subcomplexes have been shown to be separately sequestered as proteasome storage granules (PSGs) when yeast cells enter quiescence, and can be rapidly mobilized upon the resumption of cell growth. Moreover, it has been shown that association of the proteasome adaptor Ecm29 with 19S RP is increased during oxidative stress‐induced 26S disassembly in yeast and mammalian cells .…”

Selective Autophagy of the Protein Homeostasis Machinery: Ribophagy, Proteaphagy and ER-Phagy

“…Yet it was not until 2015, that selective autophagy of proteasomes was confirmed, and coined "proteaphagy" (Marshall et al, 2015). Proteaphagy has since been shown to occur in plants, yeast and mammalian cells and to be a highly regulated process mediated through distinct mechanisms depending on the physiological context (Marshall et al, 2015(Marshall et al, , 2016Waite et al, 2016;Marshall and Vierstra, 2018).…”

“…To date, proteaphagy is best understood in yeast, where it is specifically induced during both proteasome inhibition and nitrogen starvation, while carbon starvation, which also induces bulk autophagy, does not stimulate proteaphagy (Marshall and Vierstra, 2018). As in Arabidopsis, turnover of the yeast proteasome is directed by distinct, stimulus-dependent pathways, which are dependent on the core autophagy machinery (Marshall et al, 2016;Waite et al, 2016).…”

Signature activities of 20S proteasome include degradation of the ubiquitin-tag with the protein under hypoxia

“…Common stress conditions such as oxidation, temperature, ionization or toxins damage proteins, but also inevitably affect the ubiquitin-proteasome machinery. Proteasome impairment can lead to 26S accumulation in storage granules (Enenkel, 2018;Marshall and Vierstra, 2018;Peters et al, 2013), its disassembly (Bajorek et al, 2003;Livnat-Levanon et al, 2014;Wang et al, 2010), ubiquitination (Besche et al, 2014), or to proteophagy (Cohen-Kaplan et al, 2016;Marshall et al, 2015;Wen and Klionsky, 2016). Interestingly, 20S CP is relatively resistant to oxidation damage compared to 26S and persists as a stable complex under such conditions (Hohn and Grune, 2014;Reinheckel et al, 1998).…”