AMPK regulates ESCRT-dependent microautophagy of proteasomes concomitant with proteasome storage granule assembly during glucose starvation

Autoři: Jianhui Li aff001;  Michal Breker aff002;  Morven Graham aff003;  Maya Schuldiner aff002;  Mark Hochstrasser aff001
Působiště autorů: Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, Connecticut, United States of America aff001;  Department of Molecular Genetics, Weizmann Institute of Sciences, Rehovot, Israel aff002;  Center for Cellular and Molecular Imaging, School of Medicine, Yale University, New Haven, Connecticut, United States of America aff003;  Department of Molecular, Cellular, and Developmental Biology, Yale University, New Haven, Connecticut, United States of America aff004
Vyšlo v časopise: AMPK regulates ESCRT-dependent microautophagy of proteasomes concomitant with proteasome storage granule assembly during glucose starvation. PLoS Genet 15(11): e32767. doi:10.1371/journal.pgen.1008387
Kategorie: Research Article
doi: 10.1371/journal.pgen.1008387


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.

Klíčová slova:

Autophagic cell death – Fluorescence microscopy – Glucose – Homeostasis – Immunoblot analysis – Proteasomes – Vacuoles – Yeast


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