Related Experiment Video

Updated: Dec 20, 2025

A Suppressor Screen for the Characterization of Genetic Links Regulating Chronological Lifespan in Saccharomyces cerevisiae
10:39

A Suppressor Screen for the Characterization of Genetic Links Regulating Chronological Lifespan in Saccharomyces cerevisiae

Published on: September 17, 2020

6.7K

TORC1 signaling regulates cytoplasmic pH through Sir2 in yeast

Mayur Nimbadas Devare1, Yeong Hyeock Kim1, Joohye Jung1

  • 1Department of Microbiology and Molecular Biology, College of Bioscience and Biotechnology, Chungnam National University, Daejeon, Korea.

Aging Cell
|May 26, 2020
PubMed

Insights

Glucose signaling regulates yeast cell lifespan and growth by controlling Sir2 phosphorylation via TORC1 signaling and casein kinase 2 (CK2). This pathway impacts proton pump Pma1 expression and cytoplasmic pH.

Area of Science:

  • Cellular biology
  • Biochemistry
  • Yeast genetics

Background:

  • Glucose and nitrogen sources regulate TORC1 signaling, a key pathway for cell growth and lifespan.
  • Silent information regulator 2 (Sir2) is a NAD+-dependent deacetylase influencing gene expression and replicative lifespan (RLS).
  • Sir2's activity is modulated by phosphorylation, affecting its targets like the ATP-dependent proton pump Pma1.

Purpose of the Study:

  • To investigate the role of TORC1 signaling in regulating Sir2 phosphorylation.
  • To elucidate the molecular mechanisms by which TORC1 signaling controls Pma1 expression and cytoplasmic pH (pHc).
  • To identify the kinases and phosphatases involved in the TORC1-mediated regulation of Sir2 and Pma1.

Main Methods:

  • Yeast genetics: TOR1 deletion, GTR1Q65L expression, SIR2 deletion, and phospho-mutant SIR2 expression.
  • Biochemical assays: Measurement of Sir2 phosphorylation levels.
  • Physiological measurements: Assessment of Pma1 expression, cytoplasmic pH (pHc), and vacuolar pH.

Main Results:

  • TORC1 signaling inhibition (TOR1 deletion, rapamycin) decreased Pma1 expression, pHc, and vacuolar pH.
  • TORC1 signaling activation (GTR1Q65L) led to opposite phenotypes.
  • Sir2 phosphorylation is controlled by TORC1 signaling through casein kinase 2 (CK2); Sit4 and Kns1 are also required.
  • TORC1 and cAMP/PKA signaling converge on CK2 to regulate Pma1 expression via Sir2.

Conclusions:

  • TORC1 signaling regulates Pma1 expression and pHc in yeast through the CK2-Sir2 axis.
  • This regulatory axis is also influenced by the cAMP/protein kinase A (PKA) pathway.
  • Understanding this pathway provides insights into cellular homeostasis and lifespan regulation in yeast.
Keywords:
Saccharomyces cerevisiaePma1Sir2TORC1agingcytoplasmic pH

More Related Videos

Temporal Quantification of MAPK Induced Expression in Single Yeast Cells07:59

Temporal Quantification of MAPK Induced Expression in Single Yeast Cells

Published on: October 4, 2013

8.8K
G2-seq: A High Throughput Sequencing-based Technique for Identifying Late Replicating Regions of the Genome06:40

G2-seq: A High Throughput Sequencing-based Technique for Identifying Late Replicating Regions of the Genome

Published on: March 22, 2018

6.1K

Related Concept Videos

Yeast Signaling01:28

Yeast Signaling

Yeasts are single-celled organisms, but unlike bacteria, they are eukaryotes (cells with a nucleus). Cell signaling in yeast is similar to signaling in other eukaryotic cells. A ligand, such as a protein or a small molecule released from a yeast cell, attaches to a receptor on the cell surface. The binding stimulates second-messenger kinases to activate or inactivate transcription factors that further regulate gene expression. Many of the yeast intracellular signaling cascades have similar...
16.9K
PI3K/mTOR/AKT Signaling Pathway01:22

PI3K/mTOR/AKT Signaling Pathway

The mammalian target of rapamycin  (mTOR) is a serine/threonine kinase that regulates growth, proliferation, and cell survival in response to hormones, growth factors, or nutrient availability. This kinase exists in two structurally and functionally distinct forms: mTOR complex 1  (mTORC1) and mTOR complex 2  (mTORC2). The first form (mTORC1) is composed of a rapamycin-sensitive Raptor and proline-rich Akt substrate, PRAS40. In contrast,  mTORC2 consists of a...
5.1K
mTOR Signaling and Cancer Progression03:03

mTOR Signaling and Cancer Progression

The mammalian target of rapamycin or mTOR protein was discovered in 1994 due to its direct interaction with rapamycin. The protein gets its name from a yeast homolog called TOR. The mTOR protein complex in mammalian cells plays a major role in balancing anabolic processes such as the synthesis of proteins, lipids, and nucleotides and catabolic processes, such as autophagy in response to environmental cues, such as availability of nutrients and growth factors.
The mTOR pathway or the...
4.5K
Amplifying Signals via Enzymatic Cascade01:22

Amplifying Signals via Enzymatic Cascade

When a ligand binds to a cell-surface receptor, the receptor's intracellular domain changes shape, which may either activate its enzyme function or allow its binding to other molecules. The initial signal is amplified by most signal transduction pathways. This means that a single ligand molecule can activate multiple molecules of a downstream target. Proteins that relay a signal are most commonly phosphorylated at one or more sites, activating or inactivating the protein. Kinases catalyze...
16.7K
Gene Regulation During Sporulation01:17

Gene Regulation During Sporulation

Sporulation is a complex developmental process that allows certain Gram-positive bacteria, such as Bacillus subtilis and Clostridium species, to survive extreme environmental conditions. This process is tightly regulated by a series of signaling cascades and transcriptional controls, ensuring the formation of a highly resistant endospore.Sporulation is triggered by unfavorable conditions, such as nutrient depletion, and is governed by a phosphorelay system. One of the sensor kinases, such as...
349
Regulation of the Unfolded Protein Response01:31

Regulation of the Unfolded Protein Response

Inositol-requiring kinase one or IRE1 is the most conserved eukaryotic unfolded protein response (UPR) receptor. It is a type I transmembrane protein kinase receptor with a distinctive site-specific RNase activity. As the binding mechanics of the misfolded proteins with the N-terminal domain of IRE-1 are unclear, three binding models — direct, indirect, and allosteric -- are proposed for receptor activation. Nevertheless, it is known that once a misfolded protein associates with IRE1, it...
2.9K