Related Experiment Video

Updated: May 21, 2025

Monitoring Leucine-Rich Repeat Containing 8 Channel (LRRC8/VRAC) Activity Using Sensitized-Emission Förster Resonance Energy Transfer (SE-FRET)
08:54

Monitoring Leucine-Rich Repeat Containing 8 Channel (LRRC8/VRAC) Activity Using Sensitized-Emission Förster Resonance Energy Transfer (SE-FRET)

Published on: August 9, 2024

352

The Whi2-Psr1-Psr2 complex selectively regulates TORC1 and autophagy under low leucine conditions but not nitrogen

Yitao Wang1, Yang Ping1, Rui Zhou1

  • 1International College of Pharmaceutical Innovation, Soochow University, Suzhou, Jiangsu, China.

Autophagy
|March 19, 2025
PubMed

Insights

Yeast cells use amino acids and ammonia for growth. A novel Whi2-Psr1-Psr2 complex distinguishes leucine availability from general nitrogen depletion, regulating cell growth and autophagy via the target of rapamycin complex 1 (TORC1).

Area of Science:

  • Cellular biology
  • Molecular biology
  • Biochemistry

Background:

  • Amino acids and ammonia are nitrogen sources for yeast growth.
  • Depletion of nitrogen sources inhibits cell growth and activates autophagy via TORC1.
  • Previously, amino acid and ammonia depletion were thought to have similar effects on yeast.

Purpose of the Study:

  • To investigate the mechanisms by which yeast cells distinguish between different nitrogen sources.
  • To identify the molecular players involved in regulating TORC1 signaling in response to nutrient availability.
  • To elucidate the roles of Whi2, Psr1, and Psr2 in nutrient sensing and TORC1 regulation.

Main Methods:

  • Co-immunoprecipitation assays to study protein interactions.
  • Genetic analysis using yeast mutants (Whi2, Psr1, Psr2, Tor1).
  • Functional complementation assays using human HAD phosphatases.

Main Results:

  • The Whi2-Psr1-Psr2 complex specifically inhibits TORC1 under low leucine conditions, not general nitrogen depletion.
  • A parallel pathway involving Npr2 and Npr3 suppresses TORC1 under both conditions.
  • Whi2 appears to recruit Psr1 and Psr2 to TORC1, with interactions varying based on nutrient status.
  • Human HAD phosphatases can functionally substitute for yeast Psr1 and Psr2, restoring TORC1 inhibition and autophagy.

Conclusions:

  • Yeast possesses distinct pathways for sensing amino acid availability versus general nitrogen levels.
  • The Whi2-Psr1-Psr2 complex is a key regulator differentiating leucine availability from nitrogen depletion.
  • This regulatory mechanism highlights the conserved role of HAD phosphatases in nutrient signaling across species.
Keywords:
AutophagyCTDSPTORC1Whi2-Psr1-Psr2low leucinenitrogen depletion

More Related Videos

Study of Protein-protein Interactions in Autophagy Research14:08

Study of Protein-protein Interactions in Autophagy Research

Published on: September 9, 2017

9.1K
Measurements of Physiological Stress Responses in C. Elegans10:36

Measurements of Physiological Stress Responses in C. Elegans

Published on: May 21, 2020

13.8K

Related Concept Videos

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...
3.7K
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...
3.3K
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...
2.4K
Regulated Protein Degradation02:58

Regulated Protein Degradation

It is vital to regulate the activity of enzymatic as well as non-enzymatic proteins inside the cell. This can be achieved either through creating a balance between their rate of synthesis and degradation or regulating the intrinsic activity of the protein. Both these regulation mechanisms play an essential role in the normal functioning of cells.
Protein degradation plays two important roles in the cells. It helps to protect cells from misfolded or damaged proteins before they lead to a...
7.1K
Regulation of Nuclear Protein Sorting01:45

Regulation of Nuclear Protein Sorting

Nuclear protein sorting regulates nucleus composition and gene expression, crucial for determining the fate of a eukaryotic cell. Hence, the entry and exit of molecules across the nuclear envelope is a tightly controlled process. Nuclear protein sorting can be inhibited by one of the following ways: 1) masking cargo signal sequences, 2) modifying the nuclear receptor's affinity for cargo, 3) controlling the nuclear pore size, 4) retaining the cargo during its transit to the cytosol or the...
2.3K
Autophagy01:27

Autophagy

Autophagy is a self-digesting process by which a cell protects itself from threats both within and outside the cell, ranging from abnormal proteins to invading bacteria. In this process, obsolete components of the cell and invading microbes are degraded by hydrolytic enzymes active in an acidic environment of the lysosomal lumen.
An autophagic pathway consists of a series of signaling events activated in response to diverse stress and physiological conditions such as food deprivation,...
4.1K