Proteasome dynamics in response to metabolic changes

Proteasomes, essential protease complexes in protein homeostasis, adapt to metabolic changes through intracellular movements. As the executive arm of the ubiquitin-proteasome system, they selectively degrade poly-ubiquitinated proteins in an ATP-dependent process. The primary proteasome configuratio...

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Main Authors: Cordula Enenkel, Oliver P. Ernst
Format: Article
Language:English
Published: Frontiers Media S.A. 2025-03-01
Series:Frontiers in Cell and Developmental Biology
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Online Access:https://www.frontiersin.org/articles/10.3389/fcell.2025.1523382/full
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author Cordula Enenkel
Oliver P. Ernst
Oliver P. Ernst
author_facet Cordula Enenkel
Oliver P. Ernst
Oliver P. Ernst
author_sort Cordula Enenkel
collection DOAJ
description Proteasomes, essential protease complexes in protein homeostasis, adapt to metabolic changes through intracellular movements. As the executive arm of the ubiquitin-proteasome system, they selectively degrade poly-ubiquitinated proteins in an ATP-dependent process. The primary proteasome configuration involved in this degradation is the 26S proteasome, which is composed of a proteolytically active core particle flanked by two regulatory particles. In metabolically active cells, such as proliferating yeast and mammalian cancer cells, 26S proteasomes are predominantly nuclear and actively engaged in protein degradation. However, during nutrient deprivation or stress-induced quiescence, proteasome localization changes. In quiescent yeast, proteasomes initially accumulate at the nuclear envelope. During prolonged quiescence with decreased ATP levels, proteasomes exit the nucleus and are sequestered into cytoplasmic membraneless organelles, so-called proteasome storage granules (PSGs). In mammalian cells, starvation and stress trigger formation of membraneless organelles containing proteasomes and poly-ubiquitinated substrates. The proteasome condensates are motile, reversible, and contribute to stress resistance and improved fitness during aging. Proteasome condensation may involve liquid-liquid phase separation, a mechanism underlying the assembly of membraneless organelles.
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spelling doaj-art-4efbfff811fd43b78b274ff7c51691752025-08-20T02:00:47ZengFrontiers Media S.A.Frontiers in Cell and Developmental Biology2296-634X2025-03-011310.3389/fcell.2025.15233821523382Proteasome dynamics in response to metabolic changesCordula Enenkel0Oliver P. Ernst1Oliver P. Ernst2Department of Biochemistry, University of Toronto, Toronto, ON, CanadaDepartment of Biochemistry, University of Toronto, Toronto, ON, CanadaDepartment of Molecular Genetics, University of Toronto, Toronto, ON, CanadaProteasomes, essential protease complexes in protein homeostasis, adapt to metabolic changes through intracellular movements. As the executive arm of the ubiquitin-proteasome system, they selectively degrade poly-ubiquitinated proteins in an ATP-dependent process. The primary proteasome configuration involved in this degradation is the 26S proteasome, which is composed of a proteolytically active core particle flanked by two regulatory particles. In metabolically active cells, such as proliferating yeast and mammalian cancer cells, 26S proteasomes are predominantly nuclear and actively engaged in protein degradation. However, during nutrient deprivation or stress-induced quiescence, proteasome localization changes. In quiescent yeast, proteasomes initially accumulate at the nuclear envelope. During prolonged quiescence with decreased ATP levels, proteasomes exit the nucleus and are sequestered into cytoplasmic membraneless organelles, so-called proteasome storage granules (PSGs). In mammalian cells, starvation and stress trigger formation of membraneless organelles containing proteasomes and poly-ubiquitinated substrates. The proteasome condensates are motile, reversible, and contribute to stress resistance and improved fitness during aging. Proteasome condensation may involve liquid-liquid phase separation, a mechanism underlying the assembly of membraneless organelles.https://www.frontiersin.org/articles/10.3389/fcell.2025.1523382/fullmetabolic regulation of proteasome localizationproteasome condensates in membraneless organellesproteasome storage granulesprotein homeostasis (proteostasis)ubiquitin 26S-proteasome system
spellingShingle Cordula Enenkel
Oliver P. Ernst
Oliver P. Ernst
Proteasome dynamics in response to metabolic changes
Frontiers in Cell and Developmental Biology
metabolic regulation of proteasome localization
proteasome condensates in membraneless organelles
proteasome storage granules
protein homeostasis (proteostasis)
ubiquitin 26S-proteasome system
title Proteasome dynamics in response to metabolic changes
title_full Proteasome dynamics in response to metabolic changes
title_fullStr Proteasome dynamics in response to metabolic changes
title_full_unstemmed Proteasome dynamics in response to metabolic changes
title_short Proteasome dynamics in response to metabolic changes
title_sort proteasome dynamics in response to metabolic changes
topic metabolic regulation of proteasome localization
proteasome condensates in membraneless organelles
proteasome storage granules
protein homeostasis (proteostasis)
ubiquitin 26S-proteasome system
url https://www.frontiersin.org/articles/10.3389/fcell.2025.1523382/full
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AT oliverpernst proteasomedynamicsinresponsetometabolicchanges
AT oliverpernst proteasomedynamicsinresponsetometabolicchanges