Formation and dissociation of proteasome storage granules are regulated by cytosolic pH

Peters, Lee Zeev; Hazan, Rotem; Breker, Michal; Schuldiner, Maya; Ben-Aroya, Shay

doi:10.1084/jem2106oia4

Cited by 3 publications

(3 citation statements)

References 15 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Consistent with this, we found that filament formation regulates the re-growth of yeast after severe starvation. Recent findings indicate that quiescence-associated subcellular structures, such as proteasome storage granules and actin bodies, also form in a pH-dependent manner (Peters et al, 2013). Moreover, pH changes have been implicated in the regulation of stress-induced G protein signaling (Isom et al, 2013).…”

Section: Discussionmentioning

confidence: 99%

Filament formation by metabolic enzymes is a specific adaptation to an advanced state of cellular starvation

Petrovska

Nüske

Munder

et al. 2014

Preprint

198

View full text Add to dashboard Cite

One of the key questions in biology is how the metabolism of a cell responds to changes in the environment. In budding yeast, starvation causes a drop in intracellular pH, but the functional role of this pH change is not well understood. Here, we show that the enzyme glutamine synthetase (Gln1) forms filaments at low pH and that filament formation leads to enzymatic inactivation. Filament formation by Gln1 is a highly cooperative process, strongly dependent on macromolecular crowding, and involves back-to-back stacking of cylindrical homo-decamers into filaments that associate laterally to form higher order fibrils. Other metabolic enzymes also assemble into filaments at low pH. Hence, we propose that filament formation is a general mechanism to inactivate and store key metabolic enzymes during a state of advanced cellular starvation. These findings have broad implications for understanding the interplay between nutritional stress, the metabolism and the physical organization of a cell.

show abstract

Section: Discussionmentioning

confidence: 99%

Filament formation by metabolic enzymes is a specific adaptation to an advanced state of cellular starvation

Petrovska

Nüske

Munder

et al. 2014

Preprint

198

View full text Add to dashboard Cite

show abstract

“…The CP contains several proteolytic enzymes that cleave unfolded proteins into short peptides, while substrate recognition and unfolding are carried out by subunits of the RP 7,8,9 . In cells, the holoenzyme may reversibly assemble from free CPs and RPs 4 . Individual proteasomes may further assemble reversibly into distinct bodies inside the cell under certain physiological conditions 10,11,12 ; in particular they may associate with aggregates of misfolded proteins 12 .…”

Section: Introductionmentioning

confidence: 99%

Membrane potential regulates the dynamic localisation of mammalian proteasomes

Zhang

Lee

et al. 2018

Preprint

View full text Add to dashboard Cite

Proteasomes are molecular machineries responsible for regulated protein degradation and general homeostasis. The distribution of this degradation capacity is reflected by the cellular localisation of proteasomal particles. Here we combine super-resolution imaging, single-particle tracking (SPT) and single-cell patch clamp techniques to investigate the localisation and translocation of endogenous mammalian proteasomes tagged with fluorescent proteins. While proteasomes are found dispersed in the cell without distinct localisation, we detect a higher density of proteasomes in the nucleus compared to the ER and the cytosol. SPT of proteasomes revealed two populations with diffusion coefficients averaging ~4 and ~0.8 µm 2 /s. The ratio between these two populations could be altered upon changed cellular conditions. We further report that proteasomal particles translocate to the cell periphery during hyperpolarisation, while depolarisation re-localises proteasomes to the cell interior. Depolymerising microtubules or actin filaments inhibited this potential-dependent translocation. Our results suggest that at resting membrane potential proteasomes undergo diffusion-based motions, while membrane polarisation may induce cytoskeleton-dependent translocation. Fine-tuning these translocation modes can potentially dedicate proteasomes to degradation activities at distinct subcellular sites. (173 words)

show abstract

“…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).…”

mentioning

confidence: 99%

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

Sahu

Mali

Sulkshane

et al. 2019

Preprint

View full text Add to dashboard Cite

Careful removal of unwanted proteins is necessary for cell survival. The primary constitutive intracellular protease is the 26S proteasome complex, often found in equilibrium with its free catalytic subcomplex-the 20S core particle. Protein degradation by 26S is tightly regulated by prior ubiquitination of substrates, whereas 20S is amenable to substrates with an unstructured segment. Differentiating their contributions to intracellular proteolysis is challenging due to their common catalytic sites. Here, by chemically synthesizing a synoptic set of homogenous ubiquitinated proteins, we ascribe signature features to 20S function and demonstrate a unique property: degrading the ubiquitin-tag along with the target protein. Cryo-EM confirms that a ubiquitinated substrate can induce asymmetric conformational changes to 20S. Mass-spectrometry of intracellular peptidome under hypoxia and in human failing heart identifies the signature properties of 20S in cells. Moreover, the ability of 20S proteasome to clear toxic proteins rapidly, contributes to better survival under these conditions.

show abstract

Formation and dissociation of proteasome storage granules are regulated by cytosolic pH

Cited by 3 publications

References 15 publications

Filament formation by metabolic enzymes is a specific adaptation to an advanced state of cellular starvation

Filament formation by metabolic enzymes is a specific adaptation to an advanced state of cellular starvation

Membrane potential regulates the dynamic localisation of mammalian proteasomes

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

Contact Info

Product

Resources

About