Autophagy protects against de novo formation of the [<i>PSI</i><sup>+</sup>] prion in yeast

Speldewinde, Shaun H.; Doronina, Victoria A.; Grant, Chris M.

doi:10.1091/mbc.e15-08-0548

Cited by 23 publications

(25 citation statements)

References 63 publications

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“…[ PSI + ] prion formation was quantified using the ade1-14 mutant allele which confers adenine auxotrophy and prions differentiated from nuclear gene mutations by their irreversible elimination in guanidine hydrochloride (GdnHCl). The frequency of de novo [ PSI + ] prion formation in a control [ PIN + ][ psi - ] strain grown to stationary phase was estimated to be 1.1 x 10 -5 comparable to previously reported frequencies 1222. This frequency increased during CLS and a 39-fold increase was observed by day 12 (Fig.…”

Section: Resultssupporting

confidence: 86%

“…[ PSI + ] prion formation was scored by growth in the absence of adenine as described previously 12. [ PSI + ] formation was calculated based on the mean of at least three independent biological repeat experiments.…”

Section: Methodsmentioning

confidence: 99%

“…We have previously shown that autophagy protects against Sup35 aggregation and de novo [ PSI + ] prion formation 12. Autophagy is an intracellular quality control pathway that degrades damaged organelles and protein aggregates via vacuolar/lysosomal degradation 13.…”

Section: Introductionmentioning

confidence: 99%

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The frequency of yeast [PSI+] prion formation is increased during chronological ageing

Speldewinde¹,

Grant²

2017

Microb Cell

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Ageing involves a time-dependent decline in a variety of intracellular mechanisms and is associated with cellular senescence. This can be exacerbated by prion diseases which can occur in a sporadic manner, predominantly during the later stages of life. Prions are infectious, self-templating proteins responsible for several neurodegenerative diseases in mammals and several prion-forming proteins have been found in yeast. We show here that the frequency of formation of the yeast [PSI+] prion, which is the altered form of the Sup35 translation termination factor, is increased during chronological ageing. This increase is exacerbated in an atg1 mutant suggesting that autophagy normally acts to suppress age-related prion formation. We further show that cells which have switched to [PSI+] have improved viability during chronological ageing which requires active autophagy. [PSI+] stains show increased autophagic flux which correlates with increased viability and decreased levels of cellular protein aggregation. Taken together, our data indicate that the frequency of [PSI+] prion formation increases during yeast chronological ageing, and switching to the [PSI+] form can exert beneficial effects via the promotion of autophagic flux.

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Section: Resultssupporting

confidence: 86%

Section: Methodsmentioning

confidence: 99%

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The frequency of yeast [PSI+] prion formation is increased during chronological ageing

Speldewinde¹,

Grant²

2017

Microb Cell

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“…Protein quality control also influences prion formation. Mutations that disrupt autophagy, oxidative stress response, or the ubiquitin proteasome system result in increased prion formation (Allen et al, ; Chernova et al, ; Doronina, Staniforth, Speldewinde, Tuite, & Grant, ; Speldewinde, Doronina, & Grant, ), suggesting that under normal conditions, protein quality control mechanisms actively limit prion formation. Conversely, long‐term stress can also enhance prion formation.…”

Section: Sup35p As a Prionmentioning

confidence: 99%

The three faces of Sup35

Lyke

Dorweiler

Manogaran

2019

Yeast

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Sup35p is an essential protein in yeast that functions in complex with Sup45p for efficient translation termination. Although some may argue that this function is the only important attribute of Sup35p, there are two additional known facets of Sup35p's biology that may provide equally important functions for yeast; both of which involve various strategies for coping with stress. Recently, the N‐terminal and middle regions (NM) of Sup35p, which are not required for translation termination function, have been found to provide stress‐sensing abilities and facilitate the phase separation of Sup35p into biomolecular condensates in response to transient stress. Interestingly, the same NM domain is also required for Sup35p to misfold and enter into aggregates associated with the [PSI+] prion. Here, we review these three different states or “faces” of Sup35p. For each, we compare the functionality and necessity of different Sup35p domains, including the role these domains play in facilitating interactions with important protein partners, and discuss the potential ramifications that each state affords yeast cells under varying environmental conditions.

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“…There is also evidence for the involvement of other cellular machineries distinct from the chaperone network in the maintenance of prions. For instance, overexpression of the Btn2 protein involved in endosomal protein sorting cures [URE3] (57), and autophagy protects against [PSI + ] formation (65). In addition, the actin cytoskeleton and the ubiquitination systems have also been found to modulate prion propagation (reviewed in reference 66).…”

Section: Chaperones Modulate Prion Formation and Propagationmentioning

confidence: 99%

Amyloid Prions in Fungi

2016

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Prions are infectious protein polymers that have been found to cause fatal diseases in mammals. Prions have also been identified in fungi (yeast and filamentous fungi), where they behave as cytoplasmic non-Mendelian genetic elements. Fungal prions correspond in most cases to fibrillary β-sheet-rich protein aggregates termed amyloids. Fungal prion models and, in particular, yeast prions were instrumental in the description of fundamental aspects of prion structure and propagation. These models established the "protein-only" nature of prions, the physical basis of strain variation, and the role of a variety of chaperones in prion propagation and amyloid aggregate handling. Yeast and fungal prions do not necessarily correspond to harmful entities but can have adaptive roles in these organisms.

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Autophagy protects against de novo formation of the [PSI⁺] prion in yeast

Abstract: The molecular basis by which prions arise spontaneously is poorly understood. The present data point toward oxidative protein damage as one of the triggers of de novo prion formation. Autophagy functions to clear oxidatively damaged proteins before their conversion to the prion form.

Cited by 23 publications

References 63 publications

The frequency of yeast [PSI+] prion formation is increased during chronological ageing

The frequency of yeast [PSI+] prion formation is increased during chronological ageing

The three faces of Sup35

Amyloid Prions in Fungi

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Autophagy protects against de novo formation of the [PSI+] prion in yeast

Abstract: The molecular basis by which prions arise spontaneously is poorly understood. The present data point toward oxidative protein damage as one of the triggers of de novo prion formation. Autophagy functions to clear oxidatively damaged proteins before their conversion to the prion form.

Cited by 23 publications

References 63 publications

The frequency of yeast [PSI+] prion formation is increased during chronological ageing

The frequency of yeast [PSI+] prion formation is increased during chronological ageing

The three faces of Sup35

Amyloid Prions in Fungi

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Product

Resources

About

Autophagy protects against de novo formation of the [PSI⁺] prion in yeast