Abstract
The ubiquitin-proteasome system regulates numerous cellular processes and is central to protein homeostasis. In proliferating yeast and many mammalian cells, proteasomes are highly enriched in the nucleus. In carbon-starved yeast, proteasomes migrate to the cytoplasm and collect in proteasome storage granules (PSGs). PSGs dissolve and proteasomes return to the nucleus within minutes of glucose refeeding. The mechanisms by which cells regulate proteasome homeostasis under these conditions remain largely unknown. Here we show that AMP-activated protein kinase (AMPK) together with endosomal sorting complexes required for transport (ESCRTs) drive a glucose starvation-dependent microautophagy pathway that preferentially sorts aberrant proteasomes into the vacuole, thereby biasing accumulation of functional proteasomes in PSGs. The proteasome core particle (CP) and regulatory particle (RP) are regulated differently. Without AMPK, the insoluble protein deposit (IPOD) serves as an alternative site that specifically sequesters CP aggregates. Our findings reveal a novel AMPK-controlled ESCRT-mediated microautophagy mechanism in the regulation of proteasome trafficking and homeostasis under carbon starvation.
| Original language | American English |
|---|---|
| Article number | e1008387 |
| Journal | PLoS Genetics |
| Volume | 15 |
| Issue number | 11 |
| DOIs | |
| State | Published - 2019 |
| Externally published | Yes |
Bibliographical note
Funding Information:This work was supported by NIH grant GM083050 to M.H. and the Minerva foundation with funding from the Federal German Ministry for Education and Research to M.S. M.S. is an incumbent of the Dr. Gilbert Omenn and Martha Darling Professorial Chair in Molecular Genetics. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. We thank Christopher Hickey, Lauren Budenholzer, Chin Leng Cheng, and Mengwen Zhang for critical reading of the manuscript. We thank Shay Ben-Aroya for sharing the RPN5-GFPintegrated yeast deletion library for our screen.
Publisher Copyright:
© 2019 Li et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
