TORC1 signaling regulates cytoplasmic pH through Sir2 in yeast DOI Creative Commons
Mayur Nimbadas Devare, Yeong Hyeock Kim, Joohye Jung

et al.

Aging Cell, Journal Year: 2020, Volume and Issue: 19(6)

Published: May 25, 2020

Abstract Glucose controls the phosphorylation of silent information regulator 2 (Sir2), a NAD + ‐dependent protein deacetylase, which regulates expression ATP‐dependent proton pump Pma1 and replicative lifespan (RLS) in yeast. TORC1 signaling, is central cell growth lifespan, regulated by glucose as well nitrogen sources. In this study, we demonstrate that signaling Sir2 through casein kinase (CK2) to regulate PMA1 cytoplasmic pH (pHc) Inhibition either TOR1 deletion or rapamycin treatment decreased expression, pHc, vacuolar pH, whereas activation expressing constitutively active GTR1 ( Q65L) resulted opposite phenotypes. Deletion SIR2 phospho‐mutant form increased tor1 Δ mutant, suggesting functional interaction between signaling. Furthermore, KNS1 encoding LAMMER level Sir2, phosphorylation. It was also found Sit4, phosphatase 2A (PP2A)‐like phosphatase, Kns1 are required for cyclic AMP (cAMP)/protein A (PKA) pathway converge on CK2 Sir2. Taken together, these findings suggest pHc CK2–Sir2 axis, controlled cAMP/PKA

Language: Английский

Conventional and emerging roles of the energy sensor Snf1/AMPK in Saccharomyces cerevisiae DOI Creative Commons
Paola Coccetti, Raffaele Nicastro, Farida Tripodi

et al.

Microbial Cell, Journal Year: 2018, Volume and Issue: 5(11), P. 482 - 494

Published: Oct. 31, 2018

Conventional and emerging roles of the energy sensor Snf1/AMPK in Saccharomyces cerevisiae – INTRODUCTION Cell growth proliferation require a high amount for biosynthetic pathways. Cells take from nutrient intake both unicellular multicellular eukaryotes have evolved systems that allow dynamic sensing sources, mainly sugars. The class (Sucrose non-fermenting/AMP-activated protein kinase) plays key role as guardian cellular (...)

Language: Английский

Citations

76

Fungal plasma membrane domains DOI Open Access
Αλέξανδρος Αθανασόπουλος, Bruno André,

Vicky Sophianopoulou

et al.

FEMS Microbiology Reviews, Journal Year: 2019, Volume and Issue: 43(6), P. 642 - 673

Published: Aug. 25, 2019

ABSTRACT The plasma membrane (PM) performs a plethora of physiological processes, the coordination which requires spatial and temporal organization into specialized domains different sizes, stability, protein/lipid composition overall architecture. Compartmentalization PM has been particularly well studied in yeast Saccharomyces cerevisiae, where five non-overlapping have described: Membrane Compartments containing arginine permease Can1 (MCC), H+-ATPase Pma1 (MCP), TORC2 kinase (MCT), sterol transporters Ltc3/4 (MCL), cell wall stress mechanosensor Wsc1 (MCW). Additional cortical foci at fungal are sites clathrin-dependent endocytosis occurs, external pH sensing complex PAL/Rim localizes, sterol-rich found apically grown regions membranes. In this review, we summarize knowledge from several species regarding lateral segregation. We discuss mechanisms formation these domains, partitioning proteins there. Finally, roles best-known compartments, including regulation homeostasis, apical growth cells newly emerging role MCCs as starvation-protective domains.

Language: Английский

Citations

71

Regulation of Cell Death Induced by Acetic Acid in Yeasts DOI Creative Commons
Susana R. Chaves, António Rego, Vítor M. Martins

et al.

Frontiers in Cell and Developmental Biology, Journal Year: 2021, Volume and Issue: 9

Published: June 24, 2021

Acetic acid has long been considered a molecule of great interest in the yeast research field. It is mostly recognized as by-product alcoholic fermentation or product metabolism acetic and lactic bacteria, well lignocellulosic biomass pretreatment. High levels are commonly associated with arrested fermentations utilization vinegar food industry. Due to its obvious industrial processes, on mechanisms underlying impact cells increasing. In past twenty years, plethora studies have addressed intricate cascade molecular events involved cell death induced by acid, which now model regulated As such, understanding how modulates cellular functions brought about important knowledge modulable targets not only biotechnology but also biomedicine. Here, we performed comprehensive literature review compile information from published lethal concentrations shed light mechanisms. We present an historical retrospective this topic, first providing overview process including functional structural alterations, followed in-depth description pharmacological genetic regulation. mechanistic crucial both design improved biomedical strategies develop more robust resilient strains for applications, acid-induced remains fruitful open field study.

Language: Английский

Citations

49

The Plant V-ATPase DOI Creative Commons
Thorsten Seidel

Frontiers in Plant Science, Journal Year: 2022, Volume and Issue: 13

Published: June 30, 2022

V-ATPase is the dominant proton pump in plant cells. It contributes to cytosolic pH homeostasis and energizes transport processes across endomembranes of secretory pathway. Its localization trans Golgi network/early endosomes essential for vesicle transport, instance delivery cell wall components. Furthermore, it crucial response abiotic biotic stresses. The V-ATPase’s rather complex structure multiple subunit isoforms enable high structural flexibility with respect requirements different organs, developmental stages, organelles. This complexity further demands a sophisticated assembly machinery routes cells, process that still not fully understood. Regulation target phosphorylation redox-modifications but also involves interactions regulatory proteins like 14-3-3 lipid environment. by reversible assembly, as reported yeast mammalian enzyme, has be proven plants seems absent autotrophic Addressing regulation promising approach adjust its activity improved stress resistance or higher crop yield.

Language: Английский

Citations

30

TORC1 and PKA activity towards ribosome biogenesis oscillates in synchrony with the budding yeast cell cycle DOI Creative Commons
Paolo Guerra, Luc-Alban Vuillemenot, Yulan B. van Oppen

et al.

Journal of Cell Science, Journal Year: 2022, Volume and Issue: 135(18)

Published: Aug. 17, 2022

ABSTRACT Recent studies have revealed that the growth rate of budding yeast and mammalian cells varies during cell cycle. By linking a multitude signals to growth, highly conserved target rapamycin complex 1 (TORC1) protein kinase A (PKA) pathways are prime candidates for mediating dynamic coupling between division. However, measurements TORC1 PKA activity cycle still lacking. following localization dynamics two targets via time-lapse microscopy in hundreds (Saccharomyces cerevisiae) cells, we found these towards ribosome biogenesis fluctuates synchrony with even under constant external conditions. Analysis effects mutations upstream regulators suggests internal metabolic partially mediate changes. Our study reveals new aspect signaling, which will be important understanding regulation

Language: Английский

Citations

23

Reciprocal Regulation of V-ATPase and Glycolytic Pathway Elements in Health and Disease DOI Creative Commons

Summer R. Hayek,

Hallie S. Rane,

Karlett J. Parra

et al.

Frontiers in Physiology, Journal Year: 2019, Volume and Issue: 10

Published: Feb. 15, 2019

The ability of cells to adapt fluctuations in glucose availability is crucial for their survival and involves the vacuolar proton-translocating ATPase (V-ATPase), a proton pump found all eukaryotes. V-ATPase hydrolyzes ATP via its V1 domain uses energy released transport protons across membranes Vo domain. This activity critical pH homeostasis generation membrane potential that drives cellular metabolism. A number stimuli have been reported alter assembly yeast higher Glucose flux one strongest best-characterized regulators V-ATPase; this review highlights current models explaining how glycolysis are coordinated both Saccharomyces cerevisiae model fungus mammalian systems. Glucose-dependent trafficking V-ATPase, V-ATPase-dependent modulations glycolysis, recent discovery signaling through acts as molecular switch dictate anabolic versus catabolic metabolism discussed. Notably, metabolic plasticity altered glycolytic drivers numerous human pathologies, expression often disease states or can be pharmacologically manipulated treatment. overview will specifically discuss connections between cancer.

Language: Английский

Citations

41

Peroxiredoxin promotes longevity and H2O2-resistance in yeast through redox-modulation of protein kinase A DOI Creative Commons
Friederike Roger, Cecilia Picazo, Wolfgang Reiter

et al.

eLife, Journal Year: 2020, Volume and Issue: 9

Published: July 14, 2020

Peroxiredoxins are H2O2 scavenging enzymes that also carry out signaling and chaperone functions. In yeast, the major cytosolic peroxiredoxin, Tsa1 is required for both promoting resistance to extending lifespan upon caloric restriction. We show here effects these functions not by H2O2, but repressing nutrient Ras-cAMP-PKA pathway at level of protein kinase A (PKA) enzyme. stimulates sulfenylation cysteines in PKA catalytic subunit a significant proportion subunits glutathionylated on two cysteine residues. Redox modification conserved Cys243 inhibits phosphorylation Thr241 activation loop enzyme activity, preventing can overcome sensitivity Tsa1-deficient cells. Results support model aging where pathways constitute hubs integrating information from multiple aging-related conduits, including peroxiredoxin-dependent response H2O2.

Language: Английский

Citations

33

Metabolic energy conservation for fermentative product formation DOI Creative Commons
Pauline L. Folch, Markus M.M. Bisschops, Ruud A. Weusthuis

et al.

Microbial Biotechnology, Journal Year: 2021, Volume and Issue: 14(3), P. 829 - 858

Published: Jan. 13, 2021

Microbial production of bulk chemicals and biofuels from carbohydrates competes with low-cost fossil-based production. To limit costs, high titres, productivities especially yields are required. This necessitates metabolic networks involved in product formation to be redox-neutral conserve energy sustain growth maintenance. Here, we review the mechanisms available prevent unnecessary expenditure. First, an overview ATP existing sugar-based fermentation processes is presented. Substrate-level phosphorylation (SLP) kinase reactions described. Based on thermodynamics these reactions, explore whether other kinase-catalysed can applied for SLP. Generation ion-motive force another means energy. We provide examples how its generation supported by carbon-carbon double bond reduction, decarboxylation electron transfer between redox cofactors. In a wider perspective, relationship potential conservation discussed. describe input required coenzyme A (CoA) CO

Language: Английский

Citations

28

Cell cycle-linked vacuolar pH dynamics regulate amino acid homeostasis and cell growth DOI Creative Commons
Voytek Okreglak, Rachel Ling, Maria Ingaramo

et al.

Nature Metabolism, Journal Year: 2023, Volume and Issue: 5(10), P. 1803 - 1819

Published: Aug. 28, 2023

Abstract Amino acid homeostasis is critical for many cellular processes. It well established that amino acids are compartmentalized using pH gradients generated between organelles and the cytoplasm; however, dynamics of this partitioning has not been explored. Here we develop a highly sensitive reporter find major storage compartment in Saccharomyces cerevisiae , lysosome-like vacuole, alkalinizes before cell division re-acidifies as cells divide. The vacuolar require uptake extracellular activity TORC1, v-ATPase cycling specific lipid phosphatidylinositol 3,5-bisphosphate, which regulated by cyclin-dependent kinase Pho85 (CDK5 mammals). Vacuolar regulation enables sequestration mobilization from organelle, important mitochondrial function, ribosome size control. Collectively, our data provide new paradigm use dynamic pH-dependent compartmentalization during growth/division.

Language: Английский

Citations

13

The vacuolar shapes of ageing: From function to morphology DOI Creative Commons

Andreas Aufschnaiter,

Sabrina Büttner

Biochimica et Biophysica Acta (BBA) - Molecular Cell Research, Journal Year: 2019, Volume and Issue: 1866(5), P. 957 - 970

Published: Feb. 21, 2019

Cellular ageing results in accumulating damage to various macromolecules and the progressive decline of organelle function. Yeast vacuoles as well their counterpart higher eukaryotes, lysosomes, emerge central organelles lifespan determination. These acidic integrate enzymatic breakdown recycling cellular waste with nutrient sensing, storage, signalling mobilization. Establishing physical contact virtually all other organelles, serve hubs homeostasis. Studies Saccharomyces cerevisiae contributed substantially our understanding process per se multifaceted roles vacuoles/lysosomes maintenance fitness progressing age. Here, we discuss multiple vacuole during ageing, ranging from vacuolar dynamics acidification determinants function this bin, facility, reservoir integrator signalling.

Language: Английский

Citations

35