AI Article Synopsis
- TORC1 is a crucial protein complex in eukaryotic cells that connects nutrient availability to cell growth, particularly influenced by amino acids and glucose.
- The study identifies three distinct pathways for how glucose metabolism activates TORC1 in yeast: one that depends on the conversion of glucose to fructose 1,6-bisphosphate, another involving glucose to glucose 6-phosphate and mitochondrial function, and a third that operates independently of Rag GTPases requiring complete glycolysis.
- This research provides a clearer understanding of the mechanisms behind glucose-induced TORC1 activation, creating a framework for future studies on nutrient sensing.
Article Abstract
Target of Rapamycin Complex 1 (TORC1) is a conserved eukaryotic protein complex that links the presence of nutrients with cell growth. In Saccharomyces cerevisiae, TORC1 activity is positively regulated by the presence of amino acids and glucose in the medium. However, the mechanisms underlying nutrient-induced TORC1 activation remain poorly understood. By utilizing an in vivo TORC1 activation assay, we demonstrate that differential metabolism of glucose activates TORC1 through three distinct pathways in yeast. The first "canonical Rag guanosine triphosphatase (GTPase)-dependent pathway" requires conversion of glucose to fructose 1,6-bisphosphate, which activates TORC1 via the Rag GTPase heterodimer Gtr1-Gtr2. The second "non-canonical Rag GTPase-dependent pathway" requires conversion of glucose to glucose 6-phosphate, which activates TORC1 via a process that involves Gtr1-Gtr2 and mitochondrial function. The third "Rag GTPase-independent pathway" requires complete glycolysis and vacuolar ATPase reassembly for TORC1 activation. We have established a roadmap to deconstruct the link between glucose metabolism and TORC1 activation.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1016/j.celrep.2023.113205 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Knockdown of ribosomal protein L22-like 1 arrests the cell cycle and promotes apoptosis in colorectal cancer.
Cytojournal
November 2024
Key Laboratory of Microecology-Immune Regulatory Network and Related Diseases, College of Basic Medicine, Jiamusi University, Jiamusi, China.
Objective: Colorectal cancer (CRC) remains a remarkable challenge despite considerable advancements in its treatment, due to its high recurrence rate, metastasis, drug resistance, and heterogeneity. Molecular targets that can effectively inhibit CRC growth must be identified to address these challenges. Therefore, we aim to reveal the regulatory effect of ribosomal protein L22-like 1 (RPL22L1) on the proliferation and apoptosis of CRC cells and its potential mechanism.
View Article and Find Full Text PDFOscillatory autophagy induction is enabled by an updated AMPK-ULK1 regulatory wiring.
PLoS One
December 2024
Department of Genetics, ELTE Eötvös Loránd University, Budapest, Hungary.
Autophagy-dependent survival relies on a crucial oscillatory response during cellular stress. Although oscillatory behaviour is typically associated with processes like the cell cycle or circadian rhythm, emerging experimental and theoretical evidence suggests that such periodic dynamics may explain conflicting experimental results in autophagy research. In this study, we demonstrate that oscillatory behaviour in the regulation of the non-selective, stress-induced macroautophagy arises from a series of interlinked negative and positive feedback loops within the mTORC1-AMPK-ULK1 regulatory triangle.
View Article and Find Full Text PDFAutophagy Activated by Atg1 Interacts With Atg9 Promotes Biofilm Formation and Resistance of Candida albicans.
J Basic Microbiol
December 2024
Department of Endodontics, The Affiliated Stomatological Hospital of Nanjing Medical University, Nanjing, China.
Autophagy regulates the development of Candida albicans (C. albicans) biofilms and their sensitivity to antifungals. Atg1, a serine/threonine protein kinase, recruits autophagy-related proteins for autophagosome formation.
View Article and Find Full Text PDFCalmodulin enhances mTORC1 signaling by preventing TSC2-Rheb binding.
J Biol Chem
December 2024
Graduate School of Bioagricultural Sciences, Nagoya University, Furo-cho, Chikusa, Nagoya, Japan. Electronic address:
The mechanistic target of rapamycin complex 1 (mTORC1) functions as a master regulator of cell growth and proliferation. We previously demonstrated that intracellular calcium ion (Ca) concentration modulates the mTORC1 pathway via binding of the Ca sensor protein calmodulin (CaM) to tuberous sclerosis complex 2 (TSC2), a critical negative regulator of mTORC1. However, the precise molecular mechanism by which Ca/CaM modulates mTORC1 activity remains unclear.
View Article and Find Full Text PDFSTAT1 Promotes PD-L1 Activation and Tumor Growth in Lymphangioleiomyomatosis.
bioRxiv
December 2024
Division of Pulmonary, Critical Care, and Sleep Medicine, Department of Internal Medicine, University of Cincinnati; Cincinnati, OH 45267, USA.
Lymphangioleiomyomatosis (LAM) is a cystic lung disease that primarily affects women. LAM is caused by the invasion of metastatic smooth muscle-like cells into the lung parenchyma, leading to abnormal cell proliferation, lung remodeling and progressive respiratory failure. LAM cells have TSC gene mutations, which occur sporadically or in people with Tuberous Sclerosis Complex.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!