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

Cells ◽  
2021 ◽  
Vol 10 (11) ◽  
pp. 3161
Author(s):  
Mahsa Ebrahimi ◽  
Lukas Habernig ◽  
Filomena Broeskamp ◽  
Andreas Aufschnaiter ◽  
Jutta Diessl ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Multivesicular Body ◽  
Nutrient Sensing ◽  
Yeast Cells ◽  
Cyclin Dependent Kinase ◽  
Cell Cycle Exit ◽  
Negative Regulators ◽  
Term Survival ◽  
Phosphate Depletion

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.

scholarly journals Automatic synchronisation of the cell cycle in budding yeast through closed-loop feedback control

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Giansimone Perrino ◽  
Sara Napolitano ◽  
Francesca Galdi ◽  
Antonella La Regina ◽  
Davide Fiore ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Autonomous Vehicles ◽  
Genetic System ◽  
Yeast Cells ◽  
Control Engineering ◽  
Loop Feedback ◽  
Experimental Approaches ◽  
Closed Loop Feedback ◽  
Theoretical Foundations

AbstractThe cell cycle is the process by which eukaryotic cells replicate. Yeast cells cycle asynchronously with each cell in the population budding at a different time. Although there are several experimental approaches to synchronise cells, these usually work only in the short-term. Here, we build a cyber-genetic system to achieve long-term synchronisation of the cell population, by interfacing genetically modified yeast cells with a computer by means of microfluidics to dynamically change medium, and a microscope to estimate cell cycle phases of individual cells. The computer implements a controller algorithm to decide when, and for how long, to change the growth medium to synchronise the cell-cycle across the population. Our work builds upon solid theoretical foundations provided by Control Engineering. In addition to providing an avenue for yeast cell cycle synchronisation, our work shows that control engineering can be used to automatically steer complex biological processes towards desired behaviours similarly to what is currently done with robots and autonomous vehicles.

scholarly journals Cyber-yeast: Automatic synchronisation of the cell cycle in budding yeast through closed-loop feedback control

2020 ◽  
Author(s):  
Giansimone Perrino ◽  
Sara Napolitano ◽  
Francesca Galdi ◽  
Antonella La Regina ◽  
Davide Fiore ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Autonomous Vehicles ◽  
Genetic System ◽  
Yeast Cells ◽  
Control Engineering ◽  
Loop Feedback ◽  
Experimental Approaches ◽  
Closed Loop Feedback ◽  
Theoretical Foundations

ABSTRACTThe cell cycle is the process by which eukaryotic cells replicate. Yeast cells cycle asynchronously with each cell in the population budding at a different time. Although there are several experimental approaches to “synchronise” cells, these work only in the short-term. Here, we built a cyber-genetic system to achieve long-term synchronisation of the cell population, by interfacing genetically modified yeast cells with a computer by means of microfluidics to dynamically change medium, and a microscope to estimate cell cycle phases of individual cells. The computer implements a “controller” algorithm to decide when, and for how long, to change the growth medium to synchronise the cell-cycle across the population. Our work builds upon solid theoretical foundations provided by Control Engineering. In addition to providing a new avenue for yeast cell cycle synchronisation, our work shows that computers can automatically steer complex biological processes towards desired behaviours similarly to what is currently done with robots and autonomous vehicles.

scholarly journals AMPK and vacuole-associated Atg14p orchestrate μ-lipophagy for energy production and long-term survival under glucose starvation

eLife ◽  
2017 ◽  
Vol 6 ◽  
Author(s):  
Arnold Y Seo ◽  
Pick-Wei Lau ◽  
Daniel Feliciano ◽  
Prabuddha Sengupta ◽  
Mark A Le Gros ◽  
...  
Keyword(s):  
Energy Source ◽  
Energy Production ◽  
Alternative Energy ◽  
Yeast Cells ◽  
Survival Strategies ◽  
Glucose Starvation ◽  
Term Survival ◽  
Long Term Survival ◽  
Glucose Depletion

Dietary restriction increases the longevity of many organisms, but the cell signaling and organellar mechanisms underlying this capability are unclear. We demonstrate that to permit long-term survival in response to sudden glucose depletion, yeast cells activate lipid-droplet (LD) consumption through micro-lipophagy (µ-lipophagy), in which fat is metabolized as an alternative energy source. AMP-activated protein kinase (AMPK) activation triggered this pathway, which required Atg14p. More gradual glucose starvation, amino acid deprivation or rapamycin did not trigger µ-lipophagy and failed to provide the needed substitute energy source for long-term survival. During acute glucose restriction, activated AMPK was stabilized from degradation and interacted with Atg14p. This prompted Atg14p redistribution from ER exit sites onto liquid-ordered vacuole membrane domains, initiating µ-lipophagy. Our findings that activated AMPK and Atg14p are required to orchestrate µ-lipophagy for energy production in starved cells is relevant for studies on aging and evolutionary survival strategies of different organisms.

IL-7–induced proliferation of recent thymic emigrants requires activation of the PI3K pathway

Blood ◽  
2006 ◽  
Vol 109 (3) ◽  
pp. 1034-1042 ◽  
Author(s):  
Louise Swainson ◽  
Sandrina Kinet ◽  
Cedric Mongellaz ◽  
Marion Sourisseau ◽  
Telmo Henriques ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Glucose Transporter ◽  
Pi3k Pathway ◽  
High Dose ◽  
Recent Thymic Emigrants ◽  
Term Survival ◽  
Glut 1 ◽  
Cell Cycle Entry ◽  
Kinetics Of

Abstract The IL-7 cytokine promotes the survival of a diverse T-cell pool, thereby ensuring an efficient immune response. Moreover, IL-7 induces the proliferation of recent thymic emigrants (RTEs) in neonates. Here, we demonstrate that the survival and proliferative effects of IL-7 on human RTEs can be distinguished on the basis of dose as well as duration of IL-7 administration. A dose of 0.1 ng/mL IL-7 is sufficient to promote viability, whereas cell-cycle entry is observed only at doses higher than 1 ng/mL. Moreover, a short 1-hour exposure to high-dose IL-7 (10 ng/mL) induces long-term survival but continuous IL-7 exposure is necessary for optimal cell-cycle entry and proliferation. We find that distinct signaling intermediates are activated under conditions of IL-7–induced survival and proliferation; STAT5 tyrosine phosphorylation does not correlate with proliferation, whereas up-regulation of the glucose transporter Glut-1 as well as increased glucose uptake are markers of IL-7–induced cell cycle entry. Glut-1 is directly regulated by PI3K and, indeed, inhibiting PI3K activity abrogates IL-7–induced proliferation. Our finding that the survival and proliferation of RTEs are differentially modulated by the dose and kinetics of exogenous IL-7 has important implications for the clinical use of this cytokine.

scholarly journals β-Oxidation and autophagy are critical energy providers during acute glucose depletion in Saccharomyces cerevisiae

2020 ◽  
Vol 117 (22) ◽  
pp. 12239-12248 ◽  
Author(s):  
Carmen A. Weber ◽  
Karthik Sekar ◽  
Jeffrey H. Tang ◽  
Philipp Warmer ◽  
Uwe Sauer ◽  
...  
Keyword(s):  
Energy Production ◽  
Metabolic Response ◽  
Critical Energy ◽  
Yeast Cells ◽  
Glucose Starvation ◽  
Energy Status ◽  
Term Survival ◽  
Glucose Depletion ◽  
Living Organisms

The ability to tolerate and thrive in diverse environments is paramount to all living organisms, and many organisms spend a large part of their lifetime in starvation. Upon acute glucose starvation, yeast cells undergo drastic physiological and metabolic changes and reestablish a constant—although lower—level of energy production within minutes. The molecules that are rapidly metabolized to fuel energy production under these conditions are unknown. Here, we combine metabolomics and genetics to characterize the cells’ response to acute glucose depletion and identify pathways that ensure survival during starvation. We show that the ability to respire is essential for maintaining the energy status and to ensure viability during starvation. Measuring the cells’ immediate metabolic response, we find that central metabolites drastically deplete and that the intracellular AMP-to-ATP ratio strongly increases within 20 to 30 s. Furthermore, we detect changes in both amino acid and lipid metabolite levels. Consistent with this, both bulk autophagy, a process that frees amino acids, and lipid degradation via β-oxidation contribute in parallel to energy maintenance upon acute starvation. In addition, both these pathways ensure long-term survival during starvation. Thus, our results identify bulk autophagy and β-oxidation as important energy providers during acute glucose starvation.

scholarly journals FAR1 is required for oriented polarization of yeast cells in response to mating pheromones.

1995 ◽  
Vol 131 (4) ◽  
pp. 863-873 ◽  
Author(s):  
N Valtz ◽  
M Peter ◽  
I Herskowitz
Keyword(s):  
Cell Cycle ◽  
Cell Cycle Arrest ◽  
Cell Polarization ◽  
Yeast Cells ◽  
External Signal ◽  
Cyclin Dependent Kinase ◽  
Yeast Saccharomyces Cerevisiae ◽  
Mating Partner ◽  
Cycle Arrest ◽  
External Signals

Cell polarization involves specifying an area on the cell surface and organizing the cytoskeleton towards that landmark. The mechanisms by which external signals are translated into internal landmarks for polarization are poorly understood. The yeast Saccharomyces cerevisiae exhibits polarized growth during mating: the actin cytoskeleton of each cell polarizes towards its partner, presumably to allow efficient cell fusion. The external signal which determines the landmark for polarization is thought to be a gradient of peptide pheromone released by the mating partner. Here we described mutants that exhibit random polarization. Using two assays, including a direct microscope assay for orientation (Segall, J. 1993. Proc. Natl. Acad. Sci. USA. 90:8332-8337), we show that these mutants cannot locate the source of a pheromone gradient although they are able to organize their cytoskeleton. These mutants appear to be defective in mating because they are unable to locate the mating partner. They carry mutations of the FAR1 gene, denoted far1-s, and identify a new function for the Far1 protein. Its other known function is to promote cell cycle arrest during mating by inhibiting a cyclin-dependent kinase (Peter, M., and I. Herskowitz. 1994. Science (Wash. DC). 265:1228-1232). The far1-s mutants exhibit normal cell cycle arrest in response to pheromone, which suggests that Far1 protein plays two distinct roles in mating: one in cell cycle arrest and the other in orientation towards the mating partner.

scholarly journals Heterologous expression of the human cyclin-dependent kinase inhibitor p21Cip1 in the fission yeast, Schizosaccharomyces pombe reveals a role for PCNA in the chk1+ cell cycle checkpoint pathway.

1996 ◽  
Vol 7 (4) ◽  
pp. 651-662 ◽  
Author(s):  
S Tournier ◽  
D Leroy ◽  
F Goubin ◽  
B Ducommun ◽  
J S Hyams
Keyword(s):  
Cell Cycle ◽  
Fission Yeast ◽  
Kinase Inhibitor ◽  
Binding Domain ◽  
Yeast Cells ◽  
Mutant Form ◽  
Cyclin Dependent Kinase ◽  
Cyclin Dependent Kinase Inhibitor ◽  
Cell Cycle Inhibition ◽  
In Cells

Fission yeast cells expressing the human gene encoding the cyclin-dependent kinase inhibitor protein p21Cip1 were severely compromised for cell cycle progress. The degree of cell cycle inhibition was related to the level of p21Cip1 expression. Inhibited cells had a 2C DNA content and were judged by cytology and pulsed field gel electrophoresis to be in the G2 phase of the cell cycle. p21Cip1 accumulated in the nucleus and was associated with p34cdc2 and PCNA. Thus, p21Cip1 interacts with the same targets in fission yeast as in mammalian cells. Elimination of p34cdc2 binding by mutation within the cyclin-dependent kinase binding domain of p21Cip1 exaggerated the cell cycle delay phenotype. By contrast, elimination of PCNA binding by mutation within the PCNA-binding domain completely abolished the cell cycle inhibitory effects. Yeast cells expressing wild-type p21Cip1 and the mutant form that is unable to bind p34cdc2 showed enhanced sensitivity to UV. Cell cycle inhibition by p21Cip1 was largely abolished by deletion of the chk1+ gene that monitors radiation damage and was considerably enhanced in cells deleted for the rad3+ gene that monitors both DNA damage and the completion of DNA synthesis. Overexpression of PCNA also resulted in cell cycle arrest in G2 and this phenotype was also abolished by deletion of chk1+ and enhanced in cells deleted for rad3+. These results formally establish a link between PCNA and the products of the rad3+ and chk1+ checkpoint genes.

The Cyclin-Dependent Kinase Inhibitors p19Ink4d and p27Kip1 Are Coexpressed in Select Retinal Cells and Act Cooperatively to Control Cell Cycle Exit

2002 ◽  
Vol 19 (3) ◽  
pp. 359-374 ◽  
Author(s):  
Justine J. Cunningham ◽  
Edward M. Levine ◽  
Frederique Zindy ◽  
Olga Goloubeva ◽  
Martine F. Roussel ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Kinase Inhibitors ◽  
Control Cell ◽  
Cyclin Dependent Kinase ◽  
Cell Cycle Exit ◽  
Retinal Cells

scholarly journals Hog1 Targets Whi5 and Msa1 Transcription Factors To Downregulate Cyclin Expression upon Stress

2015 ◽  
Vol 35 (9) ◽  
pp. 1606-1618 ◽  
Author(s):  
Alberto González-Novo ◽  
Javier Jiménez ◽  
Josep Clotet ◽  
Mariona Nadal-Ribelles ◽  
Santiago Cavero ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Cycle Progression ◽  
Kinase Inhibitor ◽  
Yeast Cells ◽  
Cyclin Dependent Kinase ◽  
Adaptive Responses ◽  
Cycle Progression ◽  
Cellular Survival ◽  
Cyclin Dependent Kinase Inhibitor ◽  
Main Regulator

Yeast cells have developed complex mechanisms to cope with extracellular insults. An increase in external osmolarity leads to activation of the stress-activated protein kinase Hog1, which is the main regulator of adaptive responses, such as gene expression and cell cycle progression, that are essential for cellular survival. Upon osmostress, the G1-to-S transition is regulated by Hog1 through stabilization of the cyclin-dependent kinase inhibitor Sic1 and the downregulation of G1cyclin expression by an unclear mechanism. Here, we show that Hog1 interacts with and phosphorylates components of the core cell cycle transcriptional machinery such as Whi5 and the coregulator Msa1. Phosphorylation of these two transcriptional regulators by Hog1 is essential for inhibition of G1cyclin expression, for control of cell morphogenesis, and for maximal cell survival upon stress. The control of both Whi5 and Msa1 by Hog1 also revealed the necessity for proper coordination of budding and DNA replication. Thus, Hog1 regulates G1cyclin transcription upon osmostress to ensure coherent passage through Start.

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