Motif affinity and mass spectrometry proteomic approach for the discovery of cellular AMPK targets: Identification of mitochondrial fission factor as a new AMPK substrate
Open accessAbstract
AMP-activated protein kinase (AMPK) is a key cellular energy sensor and regulator of metabolic homeostasis. Although it is best known for its effects on carbohydrate and lipid metabolism, AMPK is implicated in diverse cellular processes, including mitochondrial biogenesis, autophagy, and cell growth and proliferation. To further our understanding of energy homeostasis through AMPK-dependent processes, the design and application of approaches to identify and characterise novel AMPK substrates are invaluable. Here, we report an affinity proteomicstrategy for the discovery and validation of AMPK targets using an antibody to isolate proteins containing the phospho-AMPK substrate recognition motif from hepatocytes that had been treated with pharmacological AMPK activators. We identified 57 proteins that were uniquely enriched in the activator-treated hepatocytes, but were absent in hepatocytes lacking AMPK. We focused on two candidates, cingulin and mitochondrial fission factor (MFF), and further characterised/validated them as AMPK-dependent targets by immunoblotting with phosphorylation site-specific antibodies. A small-molecule AMPK activator caused transient phosphorylation of endogenous cingulin at S137 in intestinal Caco2 cells. Multiple splice-variants of MFF appear to express in hepatocytes and we identified a common AMPK-dependent phospho-site (S129) in all the 3 predominant variants spanning the mass range and a short variant-specific site (S146). Collectively, our proteomic-based approach using a phospho-AMPK substrate antibody in combination with genetic models and selective AMPK activators will provide a powerful and reliable platform for identifying novel AMPK-dependent cellular targets.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Compound 991 robustly activates AMPK by increasing phosphorylation of downstream targets including ACC and Raptor.
“A previous study has shown that C991 robustly activates AMPK by increasing the phosphorylation of downstream targets, including ACC and Raptor32.”
From Exercise activates AMPK in mouse and human pancreatic islets to decrease senescence (2024) · cites this paper as [32]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
AMPK and mTOR regulate autophagy through direct phosphorylation of Ulk1
Kim, J., Kundu, M., Viollet, B., & Guan, K.-L. (2011) · Nature Cell Biology · doi:10.1038/ncb2152 · Cited by 7,227 · see citing works
Self-citationAMPK: a nutrient and energy sensor that maintains energy homeostasis
Hardie, D. G., Ross, F. A., & Hawley, S. A. (2012) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm3311 · Cited by 4,602 · see citing works
AMPK Phosphorylation of Raptor Mediates a Metabolic Checkpoint
Gwinn, D. M., Shackelford, D. B., Egan, D. F., Mihaylova, M. M., Mery, A., Vasquez, D. S., Turk, B. E., & Shaw, R. J. (2008) · Molecular Cell · doi:10.1016/j.molcel.2008.03.003 · Cited by 3,849 · see citing works
Phosphorylation of ULK1 (hATG1) by AMP-Activated Protein Kinase Connects Energy Sensing to Mitophagy
Egan, D. F., Shackelford, D. B., Mihaylova, M. M., Gelino, S., Kohnz, R. A., Mair, W., Vasquez, D. S., Joshi, A., Gwinn, D. M., Taylor, R., et al. (2011) · Science · doi:10.1126/science.1196371 · Cited by 2,600 · see citing works
Self-citationAMP-activated protein kinase (AMPK) action in skeletal muscle via direct phosphorylation of PGC-1α
Jäger, S., Handschin, C., St.-Pierre, J., & Spiegelman, B. M. (2007) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0705070104 · Cited by 2,491 · see citing works
AMP-activated protein kinase: an energy sensor that regulates all aspects of cell function
Hardie, D. G. (2011) · Genes & Development · doi:10.1101/gad.17420111 · Cited by 1,638 · see citing works
Steinberg, G. R., & Kemp, B. E. (2009) · Physiological Reviews · doi:10.1152/physrev.00011.2008 · Cited by 1,633 · see citing works
Self-citationAMP-Activated Protein Kinase in Metabolic Control and Insulin Signaling
Towler, M. C., & Hardie, D. G. (2007) · Circulation Research · doi:10.1161/01.res.0000256090.42690.05 · Cited by 1,248 · see citing works
Fis1, Mff, MiD49, and MiD51 mediate Drp1 recruitment in mitochondrial fission
Losón, O. C., Song, Z., Chen, H., & Chan, D. C. (2013) · Molecular Biology of the Cell · doi:10.1091/mbc.e12-10-0721 · Cited by 1,235 · see citing works
Foretz, M., Hébrard, S., Leclerc, J., Zarrinpashneh, E., Soty, M., Mithieux, G., Sakamoto, K., Andreelli, F., & Viollet, B. (2010) · Journal of Clinical Investigation · doi:10.1172/jci40671 · Cited by 1,181 · see citing works
Self-citationOtera, H., Wang, C., Cleland, M. M., Setoguchi, K., Yokota, S., Youle, R. J., & Mihara, K. (2010) · Journal of Cell Biology · doi:10.1083/jcb.201007152 · Cited by 1,110 · see citing works
Structure of mammalian AMPK and its regulation by ADP
Xiao, B., Sanders, M. J., Underwood, E., Heath, R., Mayer, F. V., Carmena, D., Jing, C., Walker, P. A., Eccleston, J. F., Haire, L. F., et al. (2011) · Nature · doi:10.1038/nature09932 · Cited by 926 · see citing works
Cantó, C., Jiang, L. Q., Deshmukh, A. S., Mataki, C., Coste, A., Lagouge, M., Zierath, J. R., & Auwerx, J. (2010) · Cell Metabolism · doi:10.1016/j.cmet.2010.02.006 · Cited by 921 · see citing works
PROSITE: a documented database using patterns and profiles as motif descriptors
Sigrist, C. J. A. (2002) · Briefings in Bioinformatics · doi:10.1093/bib/3.3.265 · Cited by 913 · see citing works
LKB1-Dependent Signaling Pathways
Alessi, D. R., Sakamoto, K., & Bayascas, J. R. (2006) · Annual Review of Biochemistry · doi:10.1146/annurev.biochem.75.103004.142702 · Cited by 783 · see citing works
Self-citationGandre-Babbe, S., & van der Bliek, A. M. (2008) · Molecular Biology of the Cell · doi:10.1091/mbc.e07-12-1287 · Cited by 769 · see citing works
AMPK is a direct adenylate charge-regulated protein kinase
Oakhill, J. S., Steel, R., Chen, Z.-P., Scott, J. W., Ling, N., Tam, S., & Kemp, B. E. (2011) · Science · doi:10.1126/science.1200094 · Cited by 612 · see citing works
Structural basis of AMPK regulation by small molecule activators
Xiao, B., Sanders, M. J., Carmena, D., Bright, N. J., Haire, L. F., Underwood, E., Patel, B. R., Heath, R. B., Walker, P. A., Hallén, S., et al. (2013) · Nature Communications · doi:10.1038/ncomms4017 · Cited by 547 · see citing works
Architecture of tight junctions and principles of molecular composition
Van Itallie, C. M., & Anderson, J. M. (2014) · Seminars in Cell & Developmental Biology · doi:10.1016/j.semcdb.2014.08.011 · Cited by 544 · see citing works
AMPK: A Key Sensor of Fuel and Energy Status in Skeletal Muscle
Hardie, D. G., & Sakamoto, K. (2006) · Physiology · doi:10.1152/physiol.00044.2005 · Cited by 519 · see citing works
Self-citationEmerging role for AS160/TBC1D4 and TBC1D1 in the regulation of GLUT4 traffic
Sakamoto, K., & Holman, G. D. (2008) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.90331.2008 · Cited by 481 · see citing works
Self-citationMechanism of Action of A-769662, a Valuable Tool for Activation of AMP-activated Protein Kinase
Göransson, O., McBride, A., Hawley, S. A., Ross, F. A., Shpiro, N., Foretz, M., Viollet, B., Hardie, D. G., & Sakamoto, K. (2007) · Journal of Biological Chemistry · doi:10.1074/jbc.m706536200 · Cited by 433 · see citing works
Self-citationO'Neill, H. M., Maarbjerg, S. J., Crane, J. D., Jeppesen, J., Jørgensen, S. B., Schertzer, J. D., Shyroka, O., Kiens, B., van Denderen, B. J., Tarnopolsky, M. A., et al. (2011) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1105062108 · Cited by 406 · see citing works
Self-citationDale, S. J., Wilson, W. A., Edelman, A. M., & Hardie, D. G. (1995) · FEBS Letters · doi:10.1016/0014-5793(95)00172-6 · Cited by 324 · see citing works
Cingulin Contains Globular and Coiled-Coil Domains and Interacts with Zo-1, Zo-2, Zo-3, and Myosin
Cordenonsi, M., D’Atri, F., Hammar, E. B., Parry, D. A. D., Kendrick‐Jones, J., Shore, D., & Citi, S. (1999) · The Journal of Cell Biology · doi:10.1083/jcb.147.7.1569 · Cited by 311 · see citing works
Sakamoto, K., Göransson, O., Hardie, D. G., & Alessi, D. R. (2004) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00074.2004 · Cited by 299 · see citing works
Self-citationScott, J. W., Norman, D., Hawley, S. A., Kontogiannis, L., & Hardie, D. G. (2002) · Journal of Molecular Biology · doi:10.1006/jmbi.2001.5316 · Cited by 179 · see citing works
The LKB1-salt-inducible kinase pathway functions as a key gluconeogenic suppressor in the liver
Patel, K. A., Foretz, M., Marion, A., Campbell, D. G., Gourlay, R., Boudaba, N., Tournier, E., Titchenell, P. M., Peggie, M. W., Deák, M., et al. (2014) · Nature Communications · doi:10.1038/ncomms5535 · Cited by 162 · see citing works
Self-citationAMPK: a cellular energy sensor primarily regulated by AMP
Gowans, G. J., & Hardie, D. G. (2014) · Biochemical Society Transactions · doi:10.1042/bst20130244 · Cited by 149 · see citing works
O'Neill, H., Lally, J., Galic, S., Thomas, M. M., Azizi, P. D., Fullerton, M., Smith, B. K., Pulinilkunnil, T., Chen, Z.-P., Samaan, M., et al. (2014) · Diabetologia · doi:10.1007/s00125-014-3273-1 · Cited by 140 · see citing works
Self-citationMechanism of Action of Compound-13: An α1-Selective Small Molecule Activator of AMPK
Hunter, R. W., Foretz, M., Bultot, L., Fullerton, M. D., Deák, M., Ross, F. A., Hawley, S. A., Shpiro, N., Viollet, B., Barron, D., et al. (2014) · Chemistry & Biology · doi:10.1016/j.chembiol.2014.05.014 · Cited by 125 · see citing works
Self-citationThe association of microtubules with tight junctions is promoted by cingulin phosphorylation by AMPK
Yano, T., Matsui, T., Tamura, A., Uji, M., & Tsukita, S. (2013) · The Journal of Cell Biology · doi:10.1083/jcb.201304194 · Cited by 120 · see citing works
AMPK Regulates ER Morphology and Function in Stressed Pancreatic β-Cells via Phosphorylation of DRP1
Wikström, J. D., Israeli, T., Bachar-Wikström, E., Swisa, A., Ariav, Y., Waiss, M., Kaganovich, D., Dor, Y., Cerasi, E., & Leibowitz, G. (2013) · Molecular Endocrinology · doi:10.1210/me.2013-1109 · Cited by 119 · see citing works
Fullerton, M. D., Hakimuddin, F., Bonen, A., & Bakovic, M. (2009) · Journal of Biological Chemistry · doi:10.1074/jbc.m109.023846 · Cited by 112 · see citing works
Lai, Y., Kviklyte, S., Vertommen, D., Lantier, L., Foretz, M., Viollet, B., Hallén, S., & Rider, M. H. (2014) · Biochemical Journal · doi:10.1042/bj20131673 · Cited by 98 · see citing works
Self-citationBeyond AICA riboside: In search of new specific AMP‐activated protein kinase activators
Guigas, B., Sakamoto, K., Taleux, N., Reyna, S. M., Musi, N., Viollet, B., & Hue, L. (2009) · IUBMB Life · doi:10.1002/iub.135 · Cited by 86 · see citing works
Self-citationEnhanced activation of cellular AMPK by dual-small molecule treatment: AICAR and A769662
Ducommun, S., Ford, R. J., Bultot, L., Deák, M., Bertrand, L., Kemp, B. E., Steinberg, G. R., & Sakamoto, K. (2014) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00672.2013 · Cited by 80 · see citing works
Self-citation
Flagged first, then by citations
Research works printed but not linked: 3
- G.J. Gowans, D.G. Hardie, Biochem. Soc. Trans. 42 (2014) 71-75.
- H.M. O'Neill, S.J. Maarbjerg, J.D. Crane, J. Jeppesen, S.B. Jorgensen, J.D. Schertzer, O. Shyroka, B. Kiens, B.J. van Denderen, M.A. Tarnopolsky, B.E. Kemp, E.A. Richter, G.R. Steinberg, Proc. Natl. Acad. Sci. U. S. A. 108 (2011) 16092-16097.
- S. Jager, C. Handschin, J. St-Pierre, B.M. Spiegelman, Proc. Natl. Acad. Sci. U. S. A. 104 (2007) 12017-12022.
Cited by
Sorted by citations
AMPK: guardian of metabolism and mitochondrial homeostasis
Herzig, S., & Shaw, R. J. (2017) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm.2017.95 · Cited by 4,094 · see citing works
Mitochondrial dynamics in health and disease: mechanisms and potential targets
Chen, W., Zhao, H., & Li, Y. (2023) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-023-01547-9 · Cited by 1,306 · see citing works
Metabolic regulation of mitochondrial dynamics
Mishra, P., & Chan, D. C. (2016) · The Journal of Cell Biology · doi:10.1083/jcb.201511036 · Cited by 1,096 · see citing works
AMP-activated protein kinase mediates mitochondrial fission in response to energy stress
Toyama, E. Q., Herzig, S., Courchet, J., Lewis, T. L., Losón, O. C., Hellberg, K., Young, N. P., Chen, H., Polleux, F., Chan, D. C., et al. (2016) · Science · doi:10.1126/science.aab4138 · Cited by 1,085 · see citing works
New insights into activation and function of the AMPK
Steinberg, G. R., & Hardie, D. G. (2022) · Nature Reviews Molecular Cell Biology · doi:10.1038/s41580-022-00547-x · Cited by 1,023 · see citing works
Self-citationAMPK: An Energy-Sensing Pathway with Multiple Inputs and Outputs
Hardie, D. G., Schaffer, B. E., & Brunet, A. (2016) · Trends in Cell Biology · doi:10.1016/j.tcb.2015.10.013 · Cited by 859 · see citing works
AMPK and TOR: The Yin and Yang of Cellular Nutrient Sensing and Growth Control
González, A., Hall, M. N., Lin, S.-C., & Hardie, D. G. (2020) · Cell Metabolism · doi:10.1016/j.cmet.2020.01.015 · Cited by 797 · see citing works
AMP-activated protein kinase: the current landscape for drug development
Steinberg, G. R., & Carling, D. (2019) · Nature Reviews Drug Discovery · doi:10.1038/s41573-019-0019-2 · Cited by 757 · see citing works
Self-citationAMPK as a Therapeutic Target for Treating Metabolic Diseases
Day, E. A., Ford, R. J., & Steinberg, G. R. (2017) · Trends in Endocrinology and Metabolism · doi:10.1016/j.tem.2017.05.004 · Cited by 620 · see citing works
Self-citationAMPK in skeletal muscle function and metabolism
Kjøbsted, R., Hingst, J. R., Fentz, J., Foretz, M., Sanz, M.-N., Pehmøller, C. K., Shum, M., Marette, A., Mounier, R., Treebak, J. T., et al. (2017) · The FASEB Journal · doi:10.1096/fj.201700442r · Cited by 496 · see citing works
Self-citationThe MAPK and AMPK signalings: interplay and implication in targeted cancer therapy
Yuan, J., Dong, X., Yap, J., & Hu, J. (2020) · Journal of Hematology & Oncology · doi:10.1186/s13045-020-00949-4 · Cited by 500 · see citing works
AMPK: restoring metabolic homeostasis over space and time
Trefts, E., & Shaw, R. J. (2021) · Molecular Cell · doi:10.1016/j.molcel.2021.08.015 · Cited by 463 · see citing works
Hoffman, N. J., Parker, B. L., Chaudhuri, R., Fisher-Wellman, K. H., Kleinert, M., Humphrey, S. J., Yang, P., Holliday, M., Trefely, S., Fazakerley, D. J., et al. (2015) · Cell Metabolism · doi:10.1016/j.cmet.2015.09.001 · Cited by 426 · see citing works
Mottillo, E. P., Desjardins, E. M., Crane, J. D., Smith, B. K., Green, A. E., Ducommun, S., Henriksen, T. I., Rebalka, I. A., Razi, A., Sakamoto, K., et al. (2016) · Cell Metabolism · doi:10.1016/j.cmet.2016.06.006 · Cited by 323 · see citing works
Self-citationAMPK, Mitochondrial Function, and Cardiovascular Disease
Wu, S., & Zou, M.-H. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21144987 · Cited by 286 · see citing works
AMPK-dependent phosphorylation is required for transcriptional activation of TFEB and TFE3
Paquette, M., El–Houjeiri, L., Zirden, L. C., Puustinen, P., Blanchette, P., Jeong, H., Dejgaard, K., Siegel, P. M., & Pause, A. (2021) · Autophagy · doi:10.1080/15548627.2021.1898748 · Cited by 260 · see citing works
AMPK signaling and its targeting in cancer progression and treatment
Hsu, C.-C., Peng, D., Cai, Z., & Lin, H. (2021) · Seminars in Cancer Biology · doi:10.1016/j.semcancer.2021.04.006 · Cited by 257 · see citing works
Cunniff, B., McKenzie, A. J., Heintz, N. H., & Howe, A. K. (2016) · Molecular Biology of the Cell · doi:10.1091/mbc.e16-05-0286 · Cited by 243 · see citing works
Causal roles of mitochondrial dynamics in longevity and healthy aging
Sharma, A., Smith, H. J., Yao, P., & Mair, W. B. (2019) · EMBO Reports · doi:10.15252/embr.201948395 · Cited by 214 · see citing works
Mitochondrial network structure homeostasis and cell death
Xie, L., Shi, F., Tan, Z., Li, Y., Bode, A. M., & Cao, Y. (2018) · Cancer Science · doi:10.1111/cas.13830 · Cited by 178 · see citing works
Metabolic Heterogeneity of Cancer Cells: An Interplay between HIF-1, GLUTs, and AMPK
Moldogazieva, N. T., Mokhosoev, I. M., & Terentiev, A. A. (2020) · Cancers · doi:10.3390/cancers12040862 · Cited by 176 · see citing works
Schaffer, B. E., Levin, R. S., Hertz, N. T., Maures, T. J., Schoof, M., Hollstein, P. E., Benayoun, B. A., Banko, M. R., Shaw, R. J., Shokat, K. M., et al. (2015) · Cell Metabolism · doi:10.1016/j.cmet.2015.09.009 · Cited by 175 · see citing works
Palikaras, K., Daskalaki, I., Markaki, M., & Tavernarakis, N. (2017) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2017.04.005 · Cited by 175 · see citing works
Seabright, A. P., Fine, N. H. F., Barlow, J. P., Lord, S. O., Musa, I., Gray, A., Bryant, J. A., Banzhaf, M., Lavery, G. G., Hardie, D. G., et al. (2020) · The FASEB Journal · doi:10.1096/fj.201903051r · Cited by 168 · see citing works
Thévenet, J., Marchi, U. D., Domingo, J. S., Christinat, N., Bultot, L., Lefebvre, G. C., Sakamoto, K., Descombes, P., Masoodi, M., & Wiederkehr, A. (2016) · The FASEB Journal · doi:10.1096/fj.201500182 · Cited by 167 · see citing works
Self-citationMitochondrial Dynamics: Fission and Fusion in Fate Determination of Mesenchymal Stem Cells
Ren, L., Chen, X., Chen, X., Li, J., Cheng, B., & Xia, J. (2020) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2020.580070 · Cited by 165 · see citing works
Proliferation and fission of peroxisomes — An update
Schrader, M., Costello, J. L., Godinho, L. F., Azadi, A. S., & Islinger, M. (2015) · Biochimica et Biophysica Acta (BBA) - Molecular Cell Research · doi:10.1016/j.bbamcr.2015.09.024 · Cited by 157 · see citing works
Johanns, M., Lai, Y., Hsu, M. F., Jacobs, R., Vertommen, D., Sande, J. V., Dumont, J. E., Woods, A., Carling, D., Hue, L., et al. (2016) · Nature Communications · doi:10.1038/ncomms10856 · Cited by 143 · see citing works
Self-citationMechanisms and roles of mitochondrial localisation and dynamics in neuronal function
Seager, R., Lee, L. J., Henley, J. M., & Wilkinson, K. A. (2020) · Neuronal Signaling · doi:10.1042/ns20200008 · Cited by 141 · see citing works
Xie, L., Shi, F., Li, Y., Li, W., Yu, X., Zhao, L., Zhou, M., Hu, J., Luo, X., Tang, M., et al. (2020) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-020-0151-9 · Cited by 133 · see citing works
Exercise and mitochondrial dynamics: keeping in shape with ROS and AMPK
Trewin, A., Berry, B., & Wojtovich, A. (2018) · Antioxidants · doi:10.3390/antiox7010007 · Cited by 129 · see citing works
Adaniya, S. M., O‐Uchi, J., Cypress, M. W., Kusakari, Y., & Jhun, B. S. (2019) · American Journal of Physiology-Cell Physiology · doi:10.1152/ajpcell.00523.2018 · Cited by 115 · see citing works
Lee, A., Kondapalli, C., Virga, D. M., Lewis, T. L., Koo, S. Y., Ashok, A., Mairet‐Coello, G., Herzig, S., Foretz, M., Viollet, B., et al. (2022) · Nature Communications · doi:10.1038/s41467-022-32130-5 · Cited by 113 · see citing works
Self-citationZheng, Q., Zhao, Y., Guo, J., Zhao, S., Fei, C., Xiao, C. W., Wu, D., Wu, L., Li, X., & Chang, C. (2018) · Cell Death and Disease · doi:10.1038/s41419-018-0552-7 · Cited by 113 · see citing works
Targeting CRL4 suppresses chemoresistant ovarian cancer growth by inducing mitophagy
Meng, Y., Qiu, L., Zeng, X., Hu, X., Zhang, Y., Wan, X., Mao, X., Wu, J., Xu, Y., Xiong, Q., et al. (2022) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-022-01253-y · Cited by 113 · see citing works
Pokharel, M. D., Flores, A. G., Marciano, D. P., Franco, M. C., Fineman, J. R., Aggarwal, S., Wang, T., & Black, S. M. (2024) · Redox Biology · doi:10.1016/j.redox.2024.103049 · Cited by 113 · see citing works
McGee, S. L., & Hargreaves, M. (2019) · Trends in Endocrinology and Metabolism · doi:10.1016/j.tem.2019.06.002 · Cited by 105 · see citing works
Mitochondrial Dysfunction in Cardiovascular Diseases: Potential Targets for Treatment
Yang, J., Guo, Q., Feng, X., Liu, Y., & Zhou, Y. (2022) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2022.841523 · Cited by 102 · see citing works
Adenosine Monophosphate (AMP)-Activated Protein Kinase: A New Target for Nutraceutical Compounds
Marín‐Aguilar, F., Pavillard, L. E., Giampieri, F., Bullón, P., & Cordero, M. D. (2017) · International Journal of Molecular Sciences · doi:10.3390/ijms18020288 · Cited by 100 · see citing works
Cellular Senescence, Mitochondrial Dysfunction, and Their Link to Cardiovascular Disease
Camacho-Encina, M., Booth, L. K., Redgrave, R. E., Folaranmi, O., Spyridopoulos, I., & Richardson, G. D. (2024) · Cells · doi:10.3390/cells13040353 · Cited by 101 · see citing works
Mitochondrial Dynamics: A Potential Therapeutic Target for Ischemic Stroke
Zhou, X., Chen, H., Wang, L., Lenahan, C., Lian, L., Ou, Y., & He, Y. (2021) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2021.721428 · Cited by 99 · see citing works
Interactive Roles for AMPK and Glycogen from Cellular Energy Sensing to Exercise Metabolism
Janzen, N. R., Whitfield, J., & Hoffman, N. J. (2018) · International Journal of Molecular Sciences · doi:10.3390/ijms19113344 · Cited by 86 · see citing works
Chen, Z., Lei, C., Wang, C., Li, N., Srivastava, M., Tang, M., Zhang, H., Choi, J. M., Jung, S. Y., Qin, J., et al. (2019) · Nature Communications · doi:10.1038/s41467-018-08004-0 · Cited by 87 · see citing works
Inositol serves as a natural inhibitor of mitochondrial fission by directly targeting AMPK
Hsu, C.-C., Zhang, X., Wang, G., Zhang, W., Cai, Z., Pan, B., Gu, H., Xu, C. S., Jin, G., Xu, X. S., et al. (2021) · Molecular Cell · doi:10.1016/j.molcel.2021.08.025 · Cited by 83 · see citing works
Salminen, A., Kaarniranta, K., & Kauppinen, A. (2016) · Biogerontology · doi:10.1007/s10522-016-9655-7 · Cited by 86 · see citing works
Exercise-Induced Mitophagy in Skeletal Muscle and Heart
Guan, Y., Drake, J. C., & Yan, Z. (2019) · Exercise and Sport Sciences Reviews · doi:10.1249/jes.0000000000000192 · Cited by 79 · see citing works
Bultot, L., Jensen, T. E., Lai, Y., Madsen, A. B., Collodet, C., Kviklyte, S., Deák, M., Yavari, A., Foretz, M., Ghaffari, S., et al. (2016) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00237.2016 · Cited by 75 · see citing works
Self-citationCollodet, C., Foretz, M., Deák, M., Bultot, L., Métairon, S., Viollet, B., Lefebvre, G., Raymond, F., Parisi, A., Civiletto, G., et al. (2019) · The FASEB Journal · doi:10.1096/fj.201900841r · Cited by 74 · see citing works
Self-citationRahman, F. A., & Quadrilatero, J. (2021) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-021-03807-9 · Cited by 76 · see citing works
MAVS is energized by Mff which senses mitochondrial metabolism via AMPK for acute antiviral immunity
Hanada, Y., Ishihara, N., Wang, L., Otera, H., Ishihara, T., Koshiba, T., Mihara, K., Ogawa, Y., & Nomura, M. (2020) · Nature Communications · doi:10.1038/s41467-020-19287-7 · Cited by 68 · see citing works
A spatiotemporal hypothesis for the regulation, role, and targeting of AMPK in prostate cancer
Khan, A., & Frigo, D. E. (2017) · Nature Reviews Urology · doi:10.1038/nrurol.2016.272 · Cited by 72 · see citing works
Traditional Chinese medicine and mitophagy: A novel approach for cardiovascular disease management
Wang, J., Zou, J., Shi, Y., Zeng, N., Guo, D., Wang, H., Zhao, C., Luan, F., Zhang, X., & Sun, J. (2024) · Phytomedicine · doi:10.1016/j.phymed.2024.155472 · Cited by 74 · see citing works
AMPK Activation Promotes Tight Junction Assembly in Intestinal Epithelial Caco-2 Cells
Olivier, S., Leclerc, J., Grenier, A., Foretz, M., Tamburini, J., & Viollet, B. (2019) · International Journal of Molecular Sciences · doi:10.3390/ijms20205171 · Cited by 70 · see citing works
Self-citationThe role of AMPK in metabolism and its influence on DNA damage repair
Szewczuk, M., Boguszewska, K., Kaźmierczak-Barańska, J., & Karwowski, B. T. (2020) · Molecular Biology Reports · doi:10.1007/s11033-020-05900-x · Cited by 66 · see citing works
Colpman, P., Dasgupta, A., & Archer, S. L. (2023) · Cells · doi:10.3390/cells12141897 · Cited by 62 · see citing works
Tanaka, Y., Yano, H., Ogasawara, S., Yoshioka, S.-I., Imamura, H., Okamoto, K., & Tsuneoka, M. (2015) · Molecular and Cellular Biology · doi:10.1128/mcb.00579-15 · Cited by 63 · see citing works
Mottillo, E. P., Desjardins, E. M., Fritzen, A. M., Zou, V. Z., Crane, J. D., Yabut, J. M., Kiens, B., Erion, D. M., Lanba, A., Granneman, J. G., et al. (2017) · Molecular Metabolism · doi:10.1016/j.molmet.2017.04.001 · Cited by 57 · see citing works
Self-citationThe influence of aerobic exercise on mitochondrial quality control in skeletal muscle
Philp, A. M., Saner, N. J., Lazarou, M., Ganley, I. G., & Philp, A. (2020) · The Journal of Physiology · doi:10.1113/jp279411 · Cited by 58 · see citing works
Novel Insights into the Anti-Aging Role of Mitophagy
(2018) · International Review of Cell and Molecular Biology · doi:10.1016/bs.ircmb.2018.05.005 · Cited by 56 · see citing works
AMP-activated protein kinase, fatty acid metabolism, and insulin sensitivity
Smith, B. K., & Steinberg, G. R. (2017) · Current Opinion in Clinical Nutrition & Metabolic Care · doi:10.1097/mco.0000000000000380 · Cited by 56 · see citing works
Self-citationMitophagy Regulates Neurodegenerative Diseases
Cen, X., Zhang, M., Zhou, M., Ye, L., & Xia, H. (2021) · Cells · doi:10.3390/cells10081876 · Cited by 58 · see citing works
Rudokas, M. W., McKay, M., Toksoy, Z., Eisen, J. N., Bögner, M., Young, L. H., & Akar, F. G. (2024) · Cardiovascular Diabetology · doi:10.1186/s12933-024-02357-1 · Cited by 55 · see citing works
The Role of Mitophagy in Skeletal Muscle Damage and Regeneration
Chatzinikita, E., Maridaki, M. D., Palikaras, K., Koutsilieris, M., & Philippou, Α. (2023) · Cells · doi:10.3390/cells12050716 · Cited by 53 · see citing works
Ahn, Y., Sabouny, R., Villa, B. R., Yee, N. C., Mychasiuk, R., Uddin, G. M., Rho, J. M., & Shutt, T. E. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21093266 · Cited by 52 · see citing works
Autophagic reliance promotes metabolic reprogramming in oncogenic KRAS-driven tumorigenesis
Lin, H., Chung, Y., Cheng, C.-T., Ouyang, C., Fu, Y., Kuo, C., Chi, K. K., Sadeghi, M., Chu, P. G., Kung, H.-J., et al. (2018) · Autophagy · doi:10.1080/15548627.2018.1450708 · Cited by 51 · see citing works
Wu, Z., Zhang, Y., Gong, X., Cheng, G., Pu, S.-B., & Cai, S. (2019) · Food & Function · doi:10.1039/c9fo02262g · Cited by 49 · see citing works
Li, D. X., Yang, S., Xing, Y., Pan, L., Zhao, R., Zhao, Y., Liu, L., & Wu, M. (2021) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2021.673839 · Cited by 48 · see citing works
The AMPK Pathway: Molecular Rejuvenation of Metabolism and Mitochondria
Malik, N., & Shaw, R. J. (2025) · Annual Review of Cell and Developmental Biology · doi:10.1146/annurev-cellbio-120420-094431 · Cited by 52 · see citing works
Liver kinase B1 regulates hepatocellular tight junction distribution and function in vivo
Porat‐Shliom, N., Tietgens, A. J., Itallie, C. M. V., Vitale-Cross, L. A., Jarník, M., Harding, O. J., Anderson, J. M., Gutkind, J. S., Weigert, R., & Arias, I. M. (2016) · Hepatology · doi:10.1002/hep.28724 · Cited by 46 · see citing works
Wangler, M. F., Chao, Y.-H., Bayat, V., Γιαγτζόγλου, Ν., Shinde, A. B., Putluri, N., Coarfa, C., Donti, T. R., Graham, B. H., Faust, J. E., et al. (2017) · PLoS Genetics · doi:10.1371/journal.pgen.1006825 · Cited by 47 · see citing works
Stein, B. D., Calzolari, D., Hellberg, K., Hu, Y., He, L., Hung, C., Toyama, E. Q., Ross, D. S., Lillemeier, B. F., Cantley, L. C., et al. (2019) · Cell Reports · doi:10.1016/j.celrep.2019.10.117 · Cited by 43 · see citing works
Mitochondrial quality surveillance: mitophagy in cardiovascular health and disease
Diao, R. Y., & Gustafsson, Å. B. (2021) · American Journal of Physiology-Cell Physiology · doi:10.1152/ajpcell.00360.2021 · Cited by 49 · see citing works
Sensing and responding to energetic stress: Evolution of the AMPK network
Craig, P. M., Moyes, C. D., & LeMoine, C. M. R. (2018) · Comparative Biochemistry and Physiology Part B: Biochemistry and Molecular Biology · doi:10.1016/j.cbpb.2017.11.001 · Cited by 46 · see citing works
AMPK at the interface of nutrient sensing, metabolic flux and energy homeostasis
Smith, T. K. T., Townsend, L. K., Smiles, W. J., Oakhill, J. S., Fullerton, M. D., & Steinberg, G. R. (2026) · Nature Metabolism · doi:10.1038/s42255-025-01442-3 · Cited by 51 · see citing works
Self-citationCX-4945 Induces Methuosis in Cholangiocarcinoma Cell Lines by a CK2-Independent Mechanism
Lertsuwan, J., Lertsuwan, K., Sawasdichai, A., Tasnawijitwong, N., Lee, K., Kitchen, P., Afford, S. C., Gaston, K., Jayaraman, P.-S., & Satayavivad, J. (2018) · Cancers · doi:10.3390/cancers10090283 · Cited by 47 · see citing works
Desjardins, E. M., Smith, B. K., Day, E. A., Ducommun, S., Sanders, M. J., Nederveen, J. P., Ford, R. J., Pinkosky, S. L., Townsend, L. K., Gutgesell, R. M., et al. (2022) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2119824119 · Cited by 44 · see citing works
Self-citationAMPK-dependent activation of the Cyclin Y/CDK16 complex controls autophagy
Dohmen, M., Krieg, S., Agalaridis, G., Zhu, X., Shehata, S. N., Pfeiffenberger, E., Amelang, J., Bütepage, M., Buerova, E., Pfaff, C. M., et al. (2020) · Nature Communications · doi:10.1038/s41467-020-14812-0 · Cited by 44 · see citing works
Self-citationCameron, K. O., & Kurumbail, R. G. (2016) · Bioorganic & Medicinal Chemistry Letters · doi:10.1016/j.bmcl.2016.09.065 · Cited by 43 · see citing works
Regulatory Roles of PINK1-Parkin and AMPK in Ubiquitin-Dependent Skeletal Muscle Mitophagy
Seabright, A. P., & Lai, Y. (2020) · Frontiers in Physiology · doi:10.3389/fphys.2020.608474 · Cited by 41 · see citing works
Adrenergic Regulation of Drp1-Driven Mitochondrial Fission in Cardiac Physio-Pathology
Jhun, B. S., O‐Uchi, J., Adaniya, S. M., Cypress, M. W., & Yoon, Y. (2018) · Antioxidants · doi:10.3390/antiox7120195 · Cited by 41 · see citing works
Huang, D., Chen, S., Xiong, D., Wang, H., Zhu, L., Wei, Y., Li, Y., & Zou, S. (2023) · Aging and Disease · doi:10.14336/ad.2023.0201 · Cited by 40 · see citing works
Form follows function for mitochondria
Wang, C., & Youle, R. J. (2016) · Nature · doi:10.1038/530288a · Cited by 40 · see citing works
Spatial control of AMPK signaling at subcellular compartments
Chauhan, A. S., Li, Z., & Gan, B. (2020) · Critical Reviews in Biochemistry and Molecular Biology · doi:10.1080/10409238.2020.1727840 · Cited by 40 · see citing works
Dandoulaki, M., Petsalaki, E., Sumpton, D. P., Zanivan, S. R., & Zachos, G. (2018) · The Journal of Cell Biology · doi:10.1083/jcb.201802102 · Cited by 40 · see citing works
Self-citationJheng, H.-F., Huang, S.-H., Kuo, H.-M., Hughes, M. W., & Tsai, Y. (2015) · Annals of the New York Academy of Sciences · doi:10.1111/nyas.12863 · Cited by 34 · see citing works
Advances of Proteomics in Novel PTM Discovery: Applications in Cancer Therapy
Wang, Y., Zhang, J., Li, B., & He, Q. (2019) · Small Methods · doi:10.1002/smtd.201900041 · Cited by 38 · see citing works
Um, J., Lee, K., Kim, Y.-Y., Lee, D., Kim, E.-M., Kim, D., & Yun, J. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms25010219 · Cited by 38 · see citing works
Redox Modifications of Proteins of the Mitochondrial Fusion and Fission Machinery
Wolf, C., Amo, V. L. D., Arndt, S., Bueno, D., Tenzer, S., Hanschmann, E.-M., Berndt, C., & Methner, A. (2020) · Cells · doi:10.3390/cells9040815 · Cited by 36 · see citing works
AMPK and Pulmonary Hypertension: Crossroads Between Vasoconstriction and Vascular Remodeling
Zhao, Q., Song, P., & Zou, M. (2021) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2021.691585 · Cited by 35 · see citing works
AMPK/MFF Activation: Role in Mitochondrial Fission and Mitophagy in Dry Eye
Peng, F., Jiang, D., Xu, W. X., Sun, Y., Zha, Z., Tan, X., Yu, J., Pan, C., Zheng, Q., & Chen, W. (2022) · Investigative Ophthalmology & Visual Science · doi:10.1167/iovs.63.12.18 · Cited by 36 · see citing works
Exercise activates AMPK in mouse and human pancreatic islets to decrease senescence
Carapeto, P., Iwasaki, K., Hela, F., Kahng, J., Alves-Wagner, A. B., Middelbeek, R. J. W., Hirshman, M. F., Rutter, G. A., Goodyear, L. J., & Aguayo-Mazzucato, C. (2024) · Nature Metabolism · doi:10.1038/s42255-024-01130-8 · Cited by 35 · see citing works
Food perception promotes phosphorylation of MFFS131 and mitochondrial fragmentation in liver
Henschke, S., Nolte, H., Magoley, J., Kleele, T., Brandt, C., Hausen, A. C., Wunderlich, C. M., Bauder, C. A., Aschauer, P., Manley, S., et al. (2024) · Science · doi:10.1126/science.adk1005 · Cited by 35 · see citing works
Energetic adaptations: Metabolic control of endocytic membrane traffic
Rahmani, S., Defferrari, M. S., Wakarchuk, W. W., & Antonescu, C. N. (2019) · Traffic · doi:10.1111/tra.12705 · Cited by 35 · see citing works
Thermogenesis and Energy Metabolism in Brown Adipose Tissue in Animals Experiencing Cold Stress
Zhang, X., Jin, X., Jiang, M., Phillips, C. J. C., & Shi, B. (2025) · International Journal of Molecular Sciences · doi:10.3390/ijms26073233 · Cited by 40 · see citing works
Martínez, J., Tarallo, D., Palma, L. M., Victoria, S., Bresque, M., Rodríguez-Bottero, S., Marmisolle, I., Escande, C., Cassina, P., Casanova, G., et al. (2019) · Biochemical Journal · doi:10.1042/bcj20190405 · Cited by 29 · see citing works
Olivier, S., Pochard, C., Ilchmann-Diounou, H., Castillo, V., Divoux, J., Alcantara, J. A., Leclerc, J., Guilmeau, S., Huet, C., Charifi, W., et al. (2021) · Molecular Metabolism · doi:10.1016/j.molmet.2021.101183 · Cited by 30 · see citing works
Self-citationThe Imbalance of Mitochondrial Fusion/Fission Drives High-Glucose-Induced Vascular Injury
Zheng, Y., Luo, A., & Liu, X. (2021) · Biomolecules · doi:10.3390/biom11121779 · Cited by 30 · see citing works
The Interplay between Cell-Extracellular Matrix Interaction and Mitochondria Dynamics in Cancer
Yanes, B., & Rainero, E. (2022) · Cancers · doi:10.3390/cancers14061433 · Cited by 30 · see citing works
Seager, R., Ramesh, N. S., Cross, S., Guo, C., Wilkinson, K. A., & Henley, J. M. (2024) · Science Advances · doi:10.1126/sciadv.adq6223 · Cited by 30 · see citing works
Testis‐specific serine kinase 3 is required for sperm morphogenesis and male fertility
Nozawa, K., Garcia, T. X., Kent, K., Leng, M., Jain, A., Malovannaya, A., Yuan, F., Yu, Z., Ikawa, M., & Matzuk, M. M. (2022) · Andrology · doi:10.1111/andr.13314 · Cited by 29 · see citing works
- Authors
- Ducommun, S., Deak, M., Sumpton, D., Ford, R. J., Núñez Galindo, A., Kussmann, M., Viollet, B., Steinberg, G. R., Foretz, M., Dayon, L., Morrice, N. A., & Sakamoto, K.
- Affiliations
- École Polytechnique Fédérale de Lausanne (CH)
- Cancer Research UK Scotland Institute (GB)
- McMaster University (CA)
- Centre National de la Recherche Scientifique (FR)
- Corresponding author
- Sakamoto, Kei
- ORCID
- Venue
- Cellular Signalling
- Publisher
- Elsevier BV
- Published
- 2015-05
- Volume
- 27
- Issue
- 5
- Pages
- 978-988
- ISSN
- 0898-6568 (ISSN-L)
- OpenAlex
- W1982521131
- Cited by
- 167
- References
- 37
- Citations by year
- 2026: 7 · 2025: 7 · 2024: 15 · 2023: 12 · 2022: 14 · 2021: 20 · 2020: 22 · 2019: 16 · 2018: 15 · 2017: 17 · 2016: 15 · 2015: 7
- FWCI
- 7.95
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Cellular Signalling (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- ENLIGHTEN (Jurnal Bimbingan dan Konseling Islam) (acceptedVersion)
- Funders
- Région Ile-de-France (CORDDIM)
- Société Francophone du Diabète (SFD)
- Canadian Institutes of Health Research (811812)
- Canadian Diabetes Association (846130)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
- Physical Sciences › Chemistry › Spectroscopy › Advanced Proteomics Techniques and Applications
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Kinase Regulation and GTPase Signaling
- Keywords
- AMPK, mitochondrial fission factor, cingulin, affinity proteomics, hepatocytes, AMPK activators, protein phosphorylation, splice variants, energy homeostasis, mitochondrial fission
- MeSH terms
- Amino Acid Sequence, Animals, Cells, Cultured, Humans, Male, Membrane Proteins, Mice, Inbred C57BL, Molecular Sequence Data, Phosphorylation, Mass Spectrometry, Caco-2 Cells, Hepatocytes, Mitochondrial Proteins, Proteomics, Mice, AMP-Activated Protein Kinases
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
