Metabolic dynamics during the cell cycle DOI Creative Commons
Andre Zylstra, Matthias Heinemann

Current Opinion in Systems Biology, Journal Year: 2022, Volume and Issue: 30, P. 100415 - 100415

Published: Feb. 11, 2022

While we have a solid understanding of the cell biological and biochemical control aspects eukaryotic growth division process, much less is known about metabolic biosynthetic dynamics during cycle. Here, review recent discoveries made at single-cell population level that show budding yeast (Saccharomyces cerevisiae) metabolism oscillates in synchrony with cycle actively dividing cells, as well independently when halted. In fact, emerging evidence suggests cycle-independent oscillations interact elements machinery via several possible mechanisms. Furthermore, reports indicate different processes exhibit temporally changing activity patterns Thus, resources are drawn from primary dynamic manner, potentially giving rise to oscillations. Finally, highlight work mammalian cells indicating similar might also exist higher eukaryotes.

Language: Английский

Reconstruction of a catalogue of genome-scale metabolic models with enzymatic constraints using GECKO 2.0 DOI Creative Commons
Iván Domenzain, Benjamín J. Sánchez,

Mihail Anton

et al.

Nature Communications, Journal Year: 2022, Volume and Issue: 13(1)

Published: June 30, 2022

Abstract Genome-scale metabolic models (GEMs) have been widely used for quantitative exploration of the relation between genotype and phenotype. Streamlined integration enzyme constraints proteomics data into such was first enabled by GECKO toolbox, allowing study phenotypes constrained protein limitations. Here, we upgrade toolbox in order to enhance with any organism a compatible GEM reconstruction. With this, enzyme-constrained budding yeasts Saccharomyces cerevisiae , Yarrowia lipolytica Kluyveromyces marxianus are generated their long-term adaptation several stress factors incorporation data. Predictions reveal that upregulation high saturation enzymes amino acid metabolism common across organisms conditions, suggesting relevance robustness contrast optimal utilization as cellular objective microbial growth under nutrient-limited conditions. The functionality is expanded an automated framework continuous version-controlled update GEMs, also producing Escherichia coli Homo sapiens . In this work, facilitate GEMs basic science, engineering synthetic biology purposes.

Language: Английский

Citations

100
Engineered Methanotrophy: A Sustainable Solution for Methane-Based Industrial Biomanufacturing DOI
Anh Duc Nguyen, Eun Yeol Lee

Trends in biotechnology, Journal Year: 2020, Volume and Issue: 39(4), P. 381 - 396

Published: Aug. 19, 2020

Language: Английский

Citations

79
Proteome-scale movements and compartment connectivity during the eukaryotic cell cycle DOI Creative Commons
Athanasios Litsios,

Benjamin Grys,

Oren Kraus

et al.

Cell, Journal Year: 2024, Volume and Issue: 187(6), P. 1490 - 1507.e21

Published: March 1, 2024

Cell cycle progression relies on coordinated changes in the composition and subcellular localization of proteome. By applying two distinct convolutional neural networks images millions live yeast cells, we resolved proteome-level dynamics both concentration during cell cycle, with resolution ∼20 classes. We show that a quarter proteome displays periodicity, proteins tending to be controlled either at level or concentration, but not both. Distinct levels protein regulation are preferentially utilized for different aspects being mostly involved control biophysical implementation program. present resource exploring global which will aid understanding fundamental biological process systems level.

Language: Английский

Citations

15
Temporal segregation of biosynthetic processes is responsible for metabolic oscillations during the budding yeast cell cycle DOI Creative Commons
Vakil Takhaveev,

Serdar Özsezen,

Edward Smith

et al.

Nature Metabolism, Journal Year: 2023, Volume and Issue: 5(2), P. 294 - 313

Published: Feb. 27, 2023

Many cell biological and biochemical mechanisms controlling the fundamental process of eukaryotic division have been identified; however, temporal dynamics biosynthetic processes during cycle are still elusive. Here, we show that key temporally segregated along cycle. Using budding yeast as a model single-cell methods to dynamically measure metabolic activity, observe two peaks in protein synthesis, G1 S/G2/M phase, whereas lipid polysaccharide synthesis only once, phase. Integrating inferred rates into thermodynamic-stoichiometric model, find this segregation causes flux changes primary metabolism, with an acceleration glucose-uptake phase-shifted oscillations oxygen carbon dioxide exchanges. Through experimental validation predictions, demonstrate metabolism oscillates cell-cycle periodicity satisfy changing demands exhibiting unexpected

Language: Английский

Citations

21
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
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
Extending the G1 phase improves the production of lipophilic compounds in yeast by boosting enzyme expression and increasing cell size DOI Creative Commons
Hao He,

Mingdong Yao,

Ying Wang

et al.

Proceedings of the National Academy of Sciences, Journal Year: 2024, Volume and Issue: 121(47)

Published: Nov. 13, 2024

Cell phase engineering can significantly impact protein synthesis and cell size, potentially enhancing the production of lipophilic products. This study investigated G1 extension on resource allocation, metabolic functions, unfolded response (UPR) in yeast, along with potential for compounds. In brief, regulation was achieved by deleting

Language: Английский

Citations

4
Reconstruction of a catalogue of genome-scale metabolic models with enzymatic constraints using GECKO 2.0 DOI Creative Commons
Iván Domenzain, Benjamín J. Sánchez,

Mihail Anton

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2021, Volume and Issue: unknown

Published: March 5, 2021

Abstract Genome-scale metabolic models (GEMs) have been widely used for quantitative exploration of the relation between genotype and phenotype. Streamlined integration enzyme constraints proteomics data into GEMs was first enabled by GECKO method, allowing study phenotypes constrained protein limitations. Here, we upgraded toolbox in order to enhance with any organism an available GEM reconstruction. With this, enzyme-constrained (ecModels) budding yeasts Saccharomyces cerevisiae, Yarrowia lipolytica Kluyveromyces marxianus were generated, aiming their long-term adaptation several stress factors incorporation data. Predictions revealed that upregulation high saturation enzymes amino acid metabolism found be common across organisms conditions, suggesting relevance robustness contrast optimal utilization as a cellular objective microbial growth under nutrient-limited conditions. The functionality further developed implementation automated framework continuous version-controlled update ecModels, which validated producing additional high-quality ecModels Escherichia coli Homo sapiens. These efforts aim facilitate basic science, engineering synthetic biology purposes.

Language: Английский

Citations

24
The yeast phosphofructokinase β-subunit has ATP-dependent RNA unwinding activity and modulates cell cycle progression DOI Creative Commons
Waleed S. Albihlal, Ana M. Matia‐González, Tobias Schmidt

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 1, 2025

Abstract Phosphofructokinase (PFK) is a rate-limiting glycolytic enzyme that also possesses an unexplored RNA binding activity. Here, we show the α- and β-subunits of yeast PFK, encoded by PFK1 PFK2 , respectively, bind hundreds mRNAs in cells, including one’s coding for proteins involved regulation mitotic cell cycle. Pkf2p directly binds Mg-ATP-dependent manner to short GA-, UC-, AU- U-rich motifs overrepresented its mRNA targets. Strikingly, Pfk2p displays directional 5’ - 3’ double-stranded unwinding activity not seen with Pfk1p. Furthermore, dynamically associates ribosomes promotes translation cycle genes. Consequently, pfk2Δ, but pfk1Δ, mutant cells severely delayed G1/S phase transition which independent enzyme’s Our results uncovered hidden function Pfk2 subunit as translational activator gene transcripts possibly through energy-dependent

Language: Английский

Citations

0
Evidence of substrate control of Cdk phosphorylation during the budding yeast cell cycle DOI Creative Commons
László Takács,

Lina Gerontogianni,

Kimberly Quililan

et al.

Cell Reports, Journal Year: 2025, Volume and Issue: 44(4), P. 115534 - 115534

Published: April 1, 2025

A series of sequential events orchestrates cell growth and division, set in motion by cyclin-dependent kinases (Cdks). In the "qualitative model" for Cdk control, order is achieved cycle stage-specific cyclins. However, single-cyclin cells retain order. an alternative "quantitative model," increasing activity triggers substrate phosphorylation at thresholds. Here, we test a key prediction from quantitative model: best substrates should be first to phosphorylated. Phosphoproteome analysis synchronous budding yeast cultures, against expectations, reveals little correlation between known vitro rates observed vivo timing. Incorporating Cdk-counteracting phosphatases that impose thresholds does not improve correlation. Instead kinase-phosphatase control (i.e., "regulator control"), our phosphoproteome patterns reveal signatures "substrate control," including substrate-defined waves. The changing behavior themselves therefore contributes ordering their during cycle.

Language: Английский

Citations

0