{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nThe AMP‐activated protein kinase (AMPK) complex is a master regulator of cellular energy homeostasis, with its catalytic subunit PRKAA1 (AMPKα1) acting as a key sensor and effector. In conditions of low ATP availability, PRKAA1‐mediated AMPK activation triggers a switch from anabolic to catabolic processes, thereby promoting energy conservation and metabolic reprogramming. This central role in sensing and restoring energy balance is reviewed in depth, highlighting its impact on cell growth, metabolism, and cytoskeletal organization."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nUnder energy stress, PRKAA1‐driven AMPK activity orchestrates adaptive cell–survival responses by modulating several regulated cell death and quality‐control mechanisms. For example, energy deprivation can inhibit ferroptosis—a form of regulated cell death triggered by lipid peroxidation—via AMPK activation."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": " AMPK also phosphorylates key downstream effectors such as BECN1 to promote lipid homeostasis and autophagy"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": ", while its direct interaction with the autophagy‐initiating kinase ULK1 is essential for the induction of autophagic flux in response to stress."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": " In neuronal cells, activation of AMPK by compounds such as resveratrol lowers amyloid‐β levels via mTOR inhibition and consequent autophagy stimulation."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "6"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn addition to its roles in energy and quality‐control signaling, PRKAA1‐mediated AMPK activity exerts potent immunomodulatory effects. Within macrophages, its activation suppresses pro‐inflammatory signals—attenuating NF‐κB activation and cytokine production—while simultaneously promoting anti‐inflammatory mediators."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "7"}]}, {"type": "t", "text": " AMPK also links nutrient sensing with inflammatory responses via SIRT1‐dependent mechanisms"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "8"}]}, {"type": "t", "text": ", and in T lymphocytes, it contributes to cytoprotective autophagy and regulates p38 MAPK pathways to mitigate senescence and support proliferative competence."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "9"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nPRKAA1‐dependent AMPK signaling is also central to the metabolic reprogramming observed in oncogenesis and other stress‐related pathologies. In cancer cells, AMPK plays dual roles by facilitating exercise‐induced metabolic adaptations"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "11"}]}, {"type": "t", "text": "and by responding to hypoxic stress through Ca²⁺/calmodulin‐dependent pathways."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "12"}]}, {"type": "t", "text": " Its suppression, for instance via ubiquitination by cancer‐specific ligases, can enhance mTOR activity and promote tumor progression"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "13"}]}, {"type": "t", "text": ", whereas its activation mediates adiponectin‐induced growth inhibition"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "14"}]}, {"type": "t", "text": "and forms feed‐forward loops with non‐coding RNAs to sustain energy stress responses."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "15"}]}, {"type": "t", "text": " Genetic association studies have even linked PRKAA1 variants to increased susceptibility to non‐cardia gastric cancer."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "16"}]}, {"type": "t", "text": " Moreover, pharmacological targeting of AMPK alters viability in glioma models"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "17"}]}, {"type": "t", "text": ", while its signaling underpins cardiovascular homeostasis"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "18"}]}, {"type": "t", "text": "and the emergence of hybrid metabolic states in cancer."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "19"}]}, {"type": "t", "text": " AMPK also supports survival during prolonged mitotic arrest"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "20"}]}, {"type": "t", "text": "and coordinates metabolic flux through the oxidative pentose phosphate pathway to favor lipogenesis."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "21"}]}, {"type": "t", "text": " Its regulatory reach extends further to the phosphorylation of non‐metabolic substrates"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "22"}]}, {"type": "t", "text": ", to the control of mitophagy via ULK1"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "23"}]}, {"type": "t", "text": ", and to mitochondrial quality control through ULK1 translocation."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "24"}]}, {"type": "t", "text": " In the context of aging and exercise, AMPK activation enhances muscle insulin sensitivity"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "25"}]}, {"type": "t", "text": ", with training modulating AMPK subunit expression"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "26"}]}, {"type": "t", "text": ", and its pharmacological re‐activation alleviating fatty liver disease"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "27"}]}, {"type": "t", "text": "as well as mitigating skin aging."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "28"}]}, {"type": "t", "text": " Furthermore, inhibition of glycolysis sensitizes cancer cells to death receptor–mediated apoptosis via AMPK signaling"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "29"}]}, {"type": "t", "text": ", and sestrin family proteins modulate AMPK responses to genotoxic stress."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "30"}]}, {"type": "t", "text": " Finally, AMPK promotes oncogenic signaling by phosphorylating Skp2 to facilitate Akt activation"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "31"}]}, {"type": "t", "text": ", and it acts downstream of Myc to trigger mitochondrial p53 stabilization and Bak‐dependent apoptosis."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "32"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nCollectively, these studies underscore the multifaceted roles of the PRKAA1‐encoded AMPKα1 subunit as a pivotal integrator of energy sensing, autophagy, inflammatory signaling, cell death, and metabolic reprogramming across diverse physiological and pathological contexts. Such versatility renders PRKAA1 a highly attractive therapeutic target for intervention in metabolic disorders, cancer, cardiovascular disease, and age‐related pathologies.\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Maria M Mihaylova, Reuben J Shaw "}, {"type": "b", "children": [{"type": "t", "text": "The AMPK signalling pathway coordinates cell growth, autophagy and metabolism."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Cell Biol (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/ncb2329"}], "href": "https://doi.org/10.1038/ncb2329"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21892142"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21892142"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Sang-Min Jeon "}, {"type": "b", "children": [{"type": "t", "text": "Regulation and function of AMPK in physiology and diseases."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Exp Mol Med (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/emm.2016.81"}], "href": "https://doi.org/10.1038/emm.2016.81"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "27416781"}], "href": "https://pubmed.ncbi.nlm.nih.gov/27416781"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Hyemin Lee, Fereshteh Zandkarimi, Yilei Zhang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Energy-stress-mediated AMPK activation inhibits ferroptosis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Cell Biol (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/s41556-020-0461-8"}], "href": "https://doi.org/10.1038/s41556-020-0461-8"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "32029897"}], "href": "https://pubmed.ncbi.nlm.nih.gov/32029897"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Xinxin Song, Shan Zhu, Pan Chen, et al. "}, {"type": "b", "children": [{"type": "t", "text": "AMPK-Mediated BECN1 Phosphorylation Promotes Ferroptosis by Directly Blocking System X"}, {"type": "a", "children": [{"type": "t", "text": "sub"}], "href": "sub"}, {"type": "t", "text": "c"}, {"type": "a", "children": [{"type": "t", "text": "/sub"}], "href": "/sub"}, {"type": "a", "children": [{"type": "t", "text": "sup"}], "href": "sup"}, {"type": "t", "text": "-"}, {"type": "a", "children": [{"type": "t", "text": "/sup"}], "href": "/sup"}, {"type": "t", "text": " Activity."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Curr Biol (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.cub.2018.05.094"}], "href": "https://doi.org/10.1016/j.cub.2018.05.094"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "30057310"}], "href": "https://pubmed.ncbi.nlm.nih.gov/30057310"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Jong Woo Lee, Sungman Park, Yoshinori Takahashi, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The association of AMPK with ULK1 regulates autophagy."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "PLoS One (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1371/journal.pone.0015394"}], "href": "https://doi.org/10.1371/journal.pone.0015394"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21072212"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21072212"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Valérie Vingtdeux, Luca Giliberto, Haitian Zhao, et al. "}, {"type": "b", "children": [{"type": "t", "text": "AMP-activated protein kinase signaling activation by resveratrol modulates amyloid-beta peptide metabolism."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M109.060061"}], "href": "https://doi.org/10.1074/jbc.M109.060061"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20080969"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20080969"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Duygu Sag, David Carling, Robert D Stout, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Adenosine 5'-monophosphate-activated protein kinase promotes macrophage polarization to an anti-inflammatory functional phenotype."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Immunol (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.4049/jimmunol.181.12.8633"}], "href": "https://doi.org/10.4049/jimmunol.181.12.8633"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19050283"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19050283"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Zhenggang Yang, Barbara B Kahn, Hang Shi, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Macrophage alpha1 AMP-activated protein kinase (alpha1AMPK) antagonizes fatty acid-induced inflammation through SIRT1."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M110.123620"}], "href": "https://doi.org/10.1074/jbc.M110.123620"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20421294"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20421294"}]}, {"type": "r", "ref": 9, "children": [{"type": "t", "text": "Griselda Herrero-Martín, Maria Høyer-Hansen, Celina García-García, et al. "}, {"type": "b", "children": [{"type": "t", "text": "TAK1 activates AMPK-dependent cytoprotective autophagy in TRAIL-treated epithelial cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "EMBO J (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/emboj.2009.8"}], "href": "https://doi.org/10.1038/emboj.2009.8"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19197243"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19197243"}]}, {"type": "r", "ref": 10, "children": [{"type": "t", "text": "Alexandre Puissant, Guillaume Robert, Nina Fenouille, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Resveratrol promotes autophagic cell death in chronic myelogenous leukemia cells via JNK-mediated p62/SQSTM1 expression and AMPK activation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cancer Res (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1158/0008-5472.CAN-09-3537"}], "href": "https://doi.org/10.1158/0008-5472.CAN-09-3537"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20103647"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20103647"}]}, {"type": "r", "ref": 11, "children": [{"type": "t", "text": "Nolan J Hoffman, Benjamin L Parker, Rima Chaudhuri, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Global Phosphoproteomic Analysis of Human Skeletal Muscle Reveals a Network of Exercise-Regulated Kinases and AMPK Substrates."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell Metab (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.cmet.2015.09.001"}], "href": "https://doi.org/10.1016/j.cmet.2015.09.001"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26437602"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26437602"}]}, {"type": "r", "ref": 12, "children": [{"type": "t", "text": "Paul T Mungai, Gregory B Waypa, Amit Jairaman, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Hypoxia triggers AMPK activation through reactive oxygen species-mediated activation of calcium release-activated calcium channels."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Cell Biol (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1128/MCB.05124-11"}], "href": "https://doi.org/10.1128/MCB.05124-11"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21670147"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21670147"}]}, {"type": "r", "ref": 13, "children": [{"type": "t", "text": "Carlos T Pineda, Saumya Ramanathan, Klementina Fon Tacer, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Degradation of AMPK by a cancer-specific ubiquitin ligase."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.cell.2015.01.034"}], "href": "https://doi.org/10.1016/j.cell.2015.01.034"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25679763"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25679763"}]}, {"type": "r", "ref": 14, "children": [{"type": "t", "text": "Mahvash Zakikhani, Ryan J O Dowling, Nahum Sonenberg, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The effects of adiponectin and metformin on prostate and colon neoplasia involve activation of AMP-activated protein kinase."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cancer Prev Res (Phila) (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1158/1940-6207.CAPR-08-0081"}], "href": "https://doi.org/10.1158/1940-6207.CAPR-08-0081"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19138981"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19138981"}]}, {"type": "r", "ref": 15, "children": [{"type": "t", "text": "Xiaowen Liu, Zhen-Dong Xiao, Leng Han, et al. "}, {"type": "b", "children": [{"type": "t", "text": "LncRNA NBR2 engages a metabolic checkpoint by regulating AMPK under energy stress."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Cell Biol (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/ncb3328"}], "href": "https://doi.org/10.1038/ncb3328"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26999735"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26999735"}]}, {"type": "r", "ref": 16, "children": [{"type": "t", "text": "Yongyong Shi, Zhibin Hu, Chen Wu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "A genome-wide association study identifies new susceptibility loci for non-cardia gastric cancer at 3q13.31 and 5p13.1."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Genet (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/ng.978"}], "href": "https://doi.org/10.1038/ng.978"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22037551"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22037551"}]}, {"type": "r", "ref": 17, "children": [{"type": "t", "text": "Xiaona Liu, Rishi Raj Chhipa, Ichiro Nakano, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The AMPK inhibitor compound C is a potent AMPK-independent antiglioma agent."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Cancer Ther (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1158/1535-7163.MCT-13-0579"}], "href": "https://doi.org/10.1158/1535-7163.MCT-13-0579"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24419061"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24419061"}]}, {"type": "r", "ref": 18, "children": [{"type": "t", "text": "Vlad G Zaha, Lawrence H Young "}, {"type": "b", "children": [{"type": "t", "text": "AMP-activated protein kinase regulation and biological actions in the heart."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Circ Res (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1161/CIRCRESAHA.111.255505"}], "href": "https://doi.org/10.1161/CIRCRESAHA.111.255505"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22935535"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22935535"}]}, {"type": "r", "ref": 19, "children": [{"type": "t", "text": "Dongya Jia, Mingyang Lu, Kwang Hwa Jung, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Elucidating cancer metabolic plasticity by coupling gene regulation with metabolic pathways."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Proc Natl Acad Sci U S A (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1073/pnas.1816391116"}], "href": "https://doi.org/10.1073/pnas.1816391116"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "30733294"}], "href": "https://pubmed.ncbi.nlm.nih.gov/30733294"}]}, {"type": "r", "ref": 20, "children": [{"type": "t", "text": "Elena Doménech, Carolina Maestre, Lorena Esteban-Martínez, et al. "}, {"type": "b", "children": [{"type": "t", "text": "AMPK and PFKFB3 mediate glycolysis and survival in response to mitophagy during mitotic arrest."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Cell Biol (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/ncb3231"}], "href": "https://doi.org/10.1038/ncb3231"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26322680"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26322680"}]}, {"type": "r", "ref": 21, "children": [{"type": "t", "text": "Ruiting Lin, Shannon Elf, Changliang Shan, et al. "}, {"type": "b", "children": [{"type": "t", "text": "6-Phosphogluconate dehydrogenase links oxidative PPP, lipogenesis and tumour growth by inhibiting LKB1-AMPK signalling."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Cell Biol (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/ncb3255"}], "href": "https://doi.org/10.1038/ncb3255"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26479318"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26479318"}]}, {"type": "r", "ref": 22, "children": [{"type": "t", "text": "Bethany E Schaffer, Rebecca S Levin, Nicholas T Hertz, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Identification of AMPK Phosphorylation Sites Reveals a Network of Proteins Involved in Cell Invasion and Facilitates Large-Scale Substrate Prediction."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell Metab (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.cmet.2015.09.009"}], "href": "https://doi.org/10.1016/j.cmet.2015.09.009"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26456332"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26456332"}]}, {"type": "r", "ref": 23, "children": [{"type": "t", "text": "Gaëtan Juban, Marielle Saclier, Houda Yacoub-Youssef, et al. "}, {"type": "b", "children": [{"type": "t", "text": "AMPK Activation Regulates LTBP4-Dependent TGF-β1 Secretion by Pro-inflammatory Macrophages and Controls Fibrosis in Duchenne Muscular Dystrophy."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell Rep (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.celrep.2018.10.077"}], "href": "https://doi.org/10.1016/j.celrep.2018.10.077"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "30463013"}], "href": "https://pubmed.ncbi.nlm.nih.gov/30463013"}]}, {"type": "r", "ref": 24, "children": [{"type": "t", "text": "Weili Tian, Wen Li, Yinqin Chen, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Phosphorylation of ULK1 by AMPK regulates translocation of ULK1 to mitochondria and mitophagy."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "FEBS Lett (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.febslet.2015.05.020"}], "href": "https://doi.org/10.1016/j.febslet.2015.05.020"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25980607"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25980607"}]}, {"type": "r", "ref": 25, "children": [{"type": "t", "text": "Antero Salminen, Kai Kaarniranta, Anu Kauppinen "}, {"type": "b", "children": [{"type": "t", "text": "Age-related changes in AMPK activation: Role for AMPK phosphatases and inhibitory phosphorylation by upstream signaling pathways."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Ageing Res Rev (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.arr.2016.04.003"}], "href": "https://doi.org/10.1016/j.arr.2016.04.003"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "27060201"}], "href": "https://pubmed.ncbi.nlm.nih.gov/27060201"}]}, {"type": "r", "ref": 26, "children": [{"type": "t", "text": "Jakob N Nielsen, Kirsty J W Mustard, Drew A Graham, et al. "}, {"type": "b", "children": [{"type": "t", "text": "5'-AMP-activated protein kinase activity and subunit expression in exercise-trained human skeletal muscle."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Appl Physiol (1985) (2003)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1152/japplphysiol.00642.2002"}], "href": "https://doi.org/10.1152/japplphysiol.00642.2002"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12391032"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12391032"}]}, {"type": "r", "ref": 27, "children": [{"type": "t", "text": "Nadia Boudaba, Allison Marion, Camille Huet, et al. "}, {"type": "b", "children": [{"type": "t", "text": "AMPK Re-Activation Suppresses Hepatic Steatosis but its Downregulation Does Not Promote Fatty Liver Development."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "EBioMedicine (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.ebiom.2018.01.008"}], "href": "https://doi.org/10.1016/j.ebiom.2018.01.008"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "29343420"}], "href": "https://pubmed.ncbi.nlm.nih.gov/29343420"}]}, {"type": "r", "ref": 28, "children": [{"type": "t", "text": "Huairui Yuan, Ying Han, Xuege Wang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "SETD2 Restricts Prostate Cancer Metastasis by Integrating EZH2 and AMPK Signaling Pathways."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cancer Cell (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.ccell.2020.05.022"}], "href": "https://doi.org/10.1016/j.ccell.2020.05.022"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "32619406"}], "href": "https://pubmed.ncbi.nlm.nih.gov/32619406"}]}, {"type": "r", "ref": 29, "children": [{"type": "t", "text": "Justin D Crane, Lauren G MacNeil, James S Lally, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Exercise-stimulated interleukin-15 is controlled by AMPK and regulates skin metabolism and aging."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Aging Cell (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1111/acel.12341"}], "href": "https://doi.org/10.1111/acel.12341"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25902870"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25902870"}]}, {"type": "r", "ref": 30, "children": [{"type": "t", "text": "L A Pradelli, M Bénéteau, C Chauvin, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Glycolysis inhibition sensitizes tumor cells to death receptors-induced apoptosis by AMP kinase activation leading to Mcl-1 block in translation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Oncogene (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/onc.2009.448"}], "href": "https://doi.org/10.1038/onc.2009.448"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19966861"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19966861"}]}, {"type": "r", "ref": 31, "children": [{"type": "t", "text": "Toran Sanli, Katja Linher-Melville, Theodoros Tsakiridis, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Sestrin2 modulates AMPK subunit expression and its response to ionizing radiation in breast cancer cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "PLoS One (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1371/journal.pone.0032035"}], "href": "https://doi.org/10.1371/journal.pone.0032035"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22363791"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22363791"}]}, {"type": "r", "ref": 32, "children": [{"type": "t", "text": "Fei Han, Chien-Feng Li, Zhen Cai, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The critical role of AMPK in driving Akt activation under stress, tumorigenesis and drug resistance."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Commun (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/s41467-018-07188-9"}], "href": "https://doi.org/10.1038/s41467-018-07188-9"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "30413706"}], "href": "https://pubmed.ncbi.nlm.nih.gov/30413706"}]}, {"type": "r", "ref": 33, "children": [{"type": "t", "text": "Anni I Nieminen, Vilja M Eskelinen, Heidi M Haikala, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Myc-induced AMPK-phospho p53 pathway activates Bak to sensitize mitochondrial apoptosis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Proc Natl Acad Sci U S A (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1073/pnas.1208530110"}], "href": "https://doi.org/10.1073/pnas.1208530110"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23589839"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23589839"}]}]}]}