ArticleThe EMBO journal2021
CARS senses cysteine deprivation to activate AMPK for cell survival.
Article in The EMBO journal, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 21 citations in OpenAlex.
- Human aminoacyl-tRNA synthetases as integrators of translation and cell signalling networks.Nature reviews. Molecular cell biology · 2026Review
- TAT-PBX1 fusion protein alleviates LPS-induced acute lung injury via AMPK-TFAM signaling activation.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Article
- Amino acids shape the metabolic and immunologic landscape in the tumor immune microenvironment: from molecular mechanisms to therapeutic strategies.Cancer biology & medicine · 2025Review
- Isoleucyl-tRNA synthetase 2 promotes pancreatic ductal adenocarcinoma proliferation and metastasis by stabilizing β-catenin.Genes & diseases · 2025Article
- The Effects of Sika Deer Antler Peptides on 3T3-L1 Preadipocytes and C57BL/6 Mice via Activating AMPK Signaling and Gut Microbiota.Molecules (Basel, Switzerland) · 2025Article
- Dysfunctional BCAA degradation triggers neuronal damage through disrupted AMPK-mitochondrial axis due to enhanced PP2Ac interaction.Communications biology · 2025Article
- Crosstalk between dysregulated amino acid sensing and glucose and lipid metabolism in colorectal cancer.Frontiers in oncology · 2025Review
- GCN2 drives diurnal patterns in the hepatic integrated stress response and maintains circadian rhythms in whole body metabolism during amino acid insufficiency.American journal of physiology. Endocrinology and metabolism · 2024Article
- Metabolomic profiling reveals decreased serum cysteine levels during gestational diabetes mellitus progression.Journal of molecular cell biology · 2024Article
- Oxidative Cysteine Post Translational Modifications Drive the Redox Code Underlying Neurodegeneration and Amyotrophic Lateral Sclerosis.Antioxidants (Basel, Switzerland) · 2024Review
- Lysosomal cystine: an unexpected alarm bell for cysteine scarcity.Trends in cell biology · 2023Article
- Nutrient sensors and their crosstalk.Experimental & molecular medicine · 2023Review
- Hierarchical inhibition of mTORC1 by glucose starvation-triggered AXIN lysosomal translocation and by AMPK.Life metabolism · 2023Article
- Review
- Mitochondrion-Localized SND1 Promotes Mitophagy and Liver Cancer Progression Through PGAM5.Frontiers in oncology · 2022Article
- AMPK CA(R)Sts a new light on amino acid sensing.The EMBO journal · 2021Article
- CARS senses cysteine deprivation to activate AMPK for cell survival.The EMBO journal · 2021Article
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Authors and funding
10 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Adenosine 5'-monophosphate (AMP)-activated protein kinase (AMPK) is an important cellular metabolite-sensing enzyme that can directly sense changes not only in ATP but also in metabolites associated with carbohydrates and fatty acids. However, less is known about whether and how AMPK senses variations in cellular amino acids. Here, we show that cysteine deficiency significantly triggers calcium/calmodulin-dependent protein kinase kinase 2 (CaMKK2)-mediated activation of AMPK. In addition, we found that CaMKK2 directly associates with cysteinyl-tRNA synthetase (CARS), which then binds to AMPKγ2 under cysteine deficiency to activate AMPK. Interestingly, we discovered that cysteine inhibits the binding of CARS to AMPKγ2, and thus, under cysteine deficiency conditions wherein the inhibitory effect of cysteine is abrogated, CARS mediates the binding of AMPK to CaMKK2, resulting in the phosphorylation and activation of AMPK by CaMKK2. Importantly, we demonstrate that blocking AMPK activation leads to cell death under cysteine-deficient conditions. In summary, our study is the first to show that CARS senses the absence of cysteine and activates AMPK through the cysteine-CARS-CaMKK2-AMPKγ2 axis, a novel adaptation strategy for cell survival under nutrient deprivation conditions.
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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.