Snd3 controls nucleus-vacuole junctions in response to glucose signaling

Tosal-Castano, Sergi; Peselj, Carlotta; Kohler, Verena; Habernig, Lukas; Berglund, Lisa Larsson; Ebrahimi, Mahsa; Vögtle, F.-Nora; Höög, Johanna L.; Andréasson, Claes; Büttner, Sabrina

doi:10.1016/j.celrep.2020.108637

Cited by 29 publications

(40 citation statements)

References 62 publications

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“…Upon cultivation on standard minimal media containing 2% glucose, cells exit cell cycle and enter quiescence as soon as glucose is exhausted [37]. To identify a setup in which cells enter stationary phase due to gradual depletion of phosphate instead of glucose but are still supplemented with sufficient phosphate to allow normal exponential growth, we monitored cellular growth across a range of phosphate concentrations.…”

Section: Phosphate Restriction Induces Longevitymentioning

confidence: 99%

Phosphate Restriction Promotes Longevity via Activation of Autophagy and the Multivesicular Body Pathway

Ebrahimi

Habernig

Broeskamp

et al. 2021

Cells

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Nutrient limitation results in an activation of autophagy in organisms ranging from yeast, nematodes and flies to mammals. Several evolutionary conserved nutrient-sensing kinases are critical for efficient adaptation of yeast cells to glucose, nitrogen or phosphate depletion, subsequent cell-cycle exit and the regulation of autophagy. Here, we demonstrate that phosphate restriction results in a prominent extension of yeast lifespan that requires the coordinated activity of autophagy and the multivesicular body pathway, enabling efficient turnover of cytoplasmic and plasma membrane cargo. While the multivesicular body pathway was essential during the early days of aging, autophagy contributed to long-term survival at later days. The cyclin-dependent kinase Pho85 was critical for phosphate restriction-induced autophagy and full lifespan extension. In contrast, when cell-cycle exit was triggered by exhaustion of glucose instead of phosphate, Pho85 and its cyclin, Pho80, functioned as negative regulators of autophagy and lifespan. The storage of phosphate in form of polyphosphate was completely dispensable to in sustaining viability under phosphate restriction. Collectively, our results identify the multifunctional, nutrient-sensing kinase Pho85 as critical modulator of longevity that differentially coordinates the autophagic response to distinct kinds of starvation.

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Section: Phosphate Restriction Induces Longevitymentioning

confidence: 99%

Phosphate Restriction Promotes Longevity via Activation of Autophagy and the Multivesicular Body Pathway

Ebrahimi

Habernig

Broeskamp

et al. 2021

Cells

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“…Whichever the case, the process will imply a deep remodeling of the contacts between the nuclear and vacuolar membranes. It is therefore possible that proteins implicated in vacuole-nucleus membranes hyper-tethering, such as Nvj1, Mdm1 and Snd3, are important players (5,8,9,15). Their study will be a key entry point to dissect the mechanism of vacuole ingression in the future.…”

Section: Discussionmentioning

confidence: 99%

“…The tether between these two membranes is actively maintained by the proteins Vac8 and Nvj1, present in the vacuolar and outer nuclear membranes, respectively (7). Helped by additional factors, such as Snd3 (8), the NVJ expands "zipper-wise" during nutritional stress, such as glucose and aminoacid shortage, and upon Target Of Rapamycin Complex (TORC) inhibition (9). This increase in the contact surface can serve to send esterified lipids for storage within Lipid Droplets (9), to increase the flux of metabolites through the mevalonate pathway (5) or to recycle non-essential nuclear components (10).…”

Section: Introductionmentioning

confidence: 99%

Negative curvature-promoting lipids instruct nuclear ingression of low autophagic potential vacuoles

Garcia

Kumanski

Elías-Villalobos

et al. 2021

Preprint

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Membrane contact sites are functional nodes at which organelles exchange information through moving ions, proteins and lipids, thus driving the reorganization of metabolic pathways and the adaptation to changing cues. The nuclear-vacuole junction of Saccharomyces cerevisiae is among the most extensive and better-known organelle contact sites, described to expand in response to various metabolic stresses. While using genotoxins with unrelated purposes, we serendipitously discovered a phenomenon that we describe as the most extreme and intimate contact ever reported between nuclei and vacuoles: the vacuole becomes completely internalized in the nucleus. We define lipids supporting negative curvature, such as phosphatidic acid and sterols, as bona-fide drivers of this event. Functionally, we purport that internalized vacuoles are low efficiency ones whose removal from the cytoplasm optimizes cargo interaction with functional vacuoles. Thus, our findings also point to nucleus-vacuole interactions as important for metabolic adaptation. Yet, rather than by inter-organelle exchanges, the underlying mechanism literally concurs with vacuolar sequestration.

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“…One examples of this is Mdm10, which forms part of the sorting and assembly machinery (SAM) complex of the mitochondrial outer membrane (Ellenrieder et al, 2016;Meisinger et al, 2004) and of the ERMES complex, a stable tether between the endoplasmic reticulum and the mitochondria (Kornmann et al, 2009). Another example is the protein Snd3, which is a component of the SND machinery, responsible for targeting proteins to the endoplasmic reticulum (Aviram et al, 2016), and was recently shown to be a part of the contact site formed between the vacuole and the nuclear endoplasmic reticulum (Tosal-Castano et al, 2021). In both of these cases, as for Vps39, the proteins engage in these moonlighting functions in MCSs, independently of the other subunits of the complex of which they form part in their other functions.…”

Section: Dynamic Formation Of the Vps41-vps3-class C Intermediate Complexmentioning

confidence: 99%

“…MCS are increasingly recognized as regulated by different metabolic pathways. For example, the nuclear-vacuolar junction changes its size in response to glucose availability (Hariri et al, 2017;Tosal-Castano et al, 2021), and the vacuole-peroxisome MCSs expands in conditions of peroxisomes proliferation (Wu et al, 2019). Whether these moonlighting proteins regulate cross-regulation of membrane contact sites with other cellular processes like for example vesicular transport (Vps39) or protein biogenesis (Tom40, Snd3, Mdm10) is an appealing model that needs to be addressed in future research.…”

Section: Dynamic Formation Of the Vps41-vps3-class C Intermediate Complexmentioning

confidence: 99%

Subunit exchange among endolysosomal tethering complexes is linked to contact site formation at the vacuole

Montoro

Duarte

Auffarth

et al. 2021

MBoC

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The hexameric HOPS (homotypic fusion and protein sorting) complex is a conserved tethering complex at the lysosome-like vacuole, where it mediates tethering and promotes all fusion events involving this organelle. The Vps39 subunit of this complex also engages in a membrane contact site between the vacuole and the mitochondria, called vCLAMP. Additionally, four subunits of HOPS are also part of the endosomal CORVET tethering complex. Here, we analyzed the partition of HOPS and CORVET subunits between the different complexes by tracing their localization and function. We find that Vps39 has a specific role in vCLAMP formation beyond tethering, and that vCLAMPs and HOPS compete for the same pool of Vps39. In agreement, we find that the CORVET subunit Vps3 can take the position of Vps39 in HOPS. This endogenous pool of a Vps3-hybrid complex is affected by Vps3 or Vps39 levels, suggesting that HOPS and CORVET assembly is dynamic. Our data shed light on how individual subunits of tethering complexes such as Vps39 can participate in other functions, while maintaining the remaining subcomplex available for its function in tethering and fusion.

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Snd3 controls nucleus-vacuole junctions in response to glucose signaling

Cited by 29 publications

References 62 publications

Phosphate Restriction Promotes Longevity via Activation of Autophagy and the Multivesicular Body Pathway

Phosphate Restriction Promotes Longevity via Activation of Autophagy and the Multivesicular Body Pathway

Negative curvature-promoting lipids instruct nuclear ingression of low autophagic potential vacuoles

Subunit exchange among endolysosomal tethering complexes is linked to contact site formation at the vacuole

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