ArticleInternational journal of molecular sciences2019
A Double Negative Feedback Loop between mTORC1 and AMPK Kinases Guarantees Precise Autophagy Induction upon Cellular Stress.
Article in International journal of molecular sciences, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 61 papers, 1 of them a synthesis that pooled it.
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Who cites it
61 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Associated Targets of the Antioxidant Cardioprotection ofBioMed research international · 2020Pooled it
- Traditional Chinese Medicine Formulas in Delaying Aging: From Theoretical Foundations to Molecular Mechanisms and Translational Perspectives.Journal of cellular and molecular medicine · 2026Review
- NFS1 activates PI3K/AKT/mTOR signaling to upregulate GPX4 expression and enhance ferroptosis resistance in osteosarcoma.Functional & integrative genomics · 2026Article
- TP53 Loss Fuels mTORC1 Activation and Autophagy Suppression to Drive Immune-Cold Colorectal Cancer.World journal of oncology · 2026Article
- Adaptive Regulation of mTOR Activity by AMPK, Akt, and ATF6 Pathways in Pi*Z Alpha-1 Antitrypsin Deficient Hepatocytes.Biomolecules · 2026Article
- Effects of Progranulin Deficiency on Inflammation and Fibrosis in the Kidneys and Liver of Diabetic Mice Fed a High-Fat Diet.Endocrinology and metabolism (Seoul, Korea) · 2026Article
- Glycophagy: molecular mechanisms, regulatory signals, and disease associations.Autophagy reports · 2026Review
- AMPK modulates a DEAH box RNA-helicase to attenuate TOR signaling and establish developmental quiescence in Caenorhabditis elegans.PLoS biology · 2025Article
- Review
- Exercise as a Metabolic Regulator: Targeting AMPK/mTOR-Autophagy Crosstalk to Counteract Sarcopenic Obesity.Aging and disease · 2025Review
- CircRNA CDR1AS promotes cardiac ischemia-reperfusion injury in mice by triggering cardiomyocyte autosis.Journal of molecular medicine (Berlin, Germany) · 2025Article
- Graphene Oxide Nanosheets Induce Mitochondrial Toxicity in Human Ovarian Granulosa Cells: Implications for Female Reproductive Health.International journal of nanomedicine · 2025Article
- Trained immunity in atherosclerosis: plasticity, metabolic-vascular axis, and AI-driven precision remodeling.Frontiers in immunology · 2025Review
- Resistance training alleviates muscle atrophy and muscle dysfunction by reducing inflammation and regulating compromised autophagy in aged skeletal muscle.Frontiers in immunology · 2025Article
- TRIM22 functions as a scaffold protein for autophagy initiation.Animal cells and systems · 2025Article
- Modulating Autophagy in Osteoarthritis: Exploring Emerging Therapeutic Drug Targets.International journal of molecular sciences · 2024Review
- Anti-Diabetic Therapies and Cancer: From Bench to Bedside.Biomolecules · 2024Review
- Mitochondrial Quality Control in Alzheimer's Disease: Insights fromAntioxidants (Basel, Switzerland) · 2024Review
- SFRP4 promotes autophagy and blunts FSH responsiveness through inhibition of AKT signaling in ovarian granulosa cells.Cell communication and signaling : CCS · 2024Article
- LncRNA PTENP1/miR-21/PTEN Axis Modulates EMT and Drug Resistance in Cancer: Dynamic Boolean Modeling for Cell Fates in DNA Damage Response.International journal of molecular sciences · 2024Article
1 more citing papers are in PubMed but not listed here.
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6 authors.
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Abstract
Cellular homeostasis is controlled by an evolutionary conserved cellular digestive process called autophagy. This mechanism is tightly regulated by the two sensor elements called mTORC1 and AMPK. mTORC1 is one of the master regulators of proteostasis, while AMPK maintains cellular energy homeostasis. AMPK is able to promote autophagy by phosphorylating ULK1, the key inducer of autophagosome formation, while mTORC1 downregulates the self-eating process via ULK1 under nutrient rich conditions. We claim that the feedback loops of the AMPK-mTORC1-ULK1 regulatory triangle guarantee the appropriate response mechanism when nutrient and/or energy supply changes. In our opinion, there is an essential double negative feedback loop between mTORC1 and AMPK. Namely, not only does AMPK downregulate mTORC1, but mTORC1 also inhibits AMPK and this inhibition is required to keep AMPK inactive at physiological conditions. The aim of the present study was to explore the dynamical characteristic of AMPK regulation upon various cellular stress events. We approached our scientific analysis from a systems biology perspective by incorporating both theoretical and molecular biological techniques. In this study, we confirmed that AMPK is essential to promote autophagy, but is not sufficient to maintain it. AMPK activation is followed by ULK1 induction, where protein has a key role in keeping autophagy active. ULK1-controlled autophagy is always preceded by AMPK activation. With both ULK1 depletion and mTORC1 hyper-activation (i.e., TSC1/2 downregulation), we demonstrate that a double negative feedback loop between AMPK and mTORC1 is crucial for the proper dynamic features of the control network. Our computer simulations have further proved the dynamical characteristic of AMPK-mTORC1-ULK1 controlled cellular nutrient sensing.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.