The DOI matches its Crossref record; 35 of the 35 references it cites were found in a registry or an index.
Fructose-1,6-bisphosphate and aldolase mediate glucose sensing by AMPK
Open accessAbstract
The major energy source for most cells is glucose, from which ATP is generated via glycolysis and/or oxidative metabolism. Glucose deprivation activates AMP-activated protein kinase (AMPK), but it is unclear whether this activation occurs solely via changes in AMP or ADP, the classical activators of AMPK. Here, we describe an AMP/ADP-independent mechanism that triggers AMPK activation by sensing the absence of fructose-1,6-bisphosphate (FBP), with AMPK being progressively activated as extracellular glucose and intracellular FBP decrease. When unoccupied by FBP, aldolases promote the formation of a lysosomal complex containing at least v-ATPase, ragulator, axin, liver kinase B1 (LKB1) and AMPK, which has previously been shown to be required for AMPK activation. Knockdown of aldolases activates AMPK even in cells with abundant glucose, whereas the catalysis-defective D34S aldolase mutant, which still binds FBP, blocks AMPK activation. Cell-free reconstitution assays show that addition of FBP disrupts the association of axin and LKB1 with v-ATPase and ragulator. Importantly, in some cell types AMP/ATP and ADP/ATP ratios remain unchanged during acute glucose starvation, and intact AMP-binding sites on AMPK are not required for AMPK activation. These results establish that aldolase, as well as being a glycolytic enzyme, is a sensor of glucose availability that regulates AMPK.
Overview
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
Verification
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.
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
Repertoires of Autophagy in the Pathogenesis of Ocular Diseases
Li, Y.-J., Jiang, Q., Cao, G.-F., Yao, J., & Yan, B. (2015) · Cellular Physiology and Biochemistry · doi:10.1159/000373980 · Cited by 16,304
Genome engineering using the CRISPR-Cas9 system
Ran, F. A., Hsu, P. D., Wright, J., Agarwala, V., Scott, D. A., & Zhang, F. (2013) · Nature Protocols · doi:10.1038/nprot.2013.143 · Cited by 11,133
Delivery of siRNA to the mouse brain by systemic injection of targeted exosomes
Alvarez-Erviti, L., Seow, Y., Yin, H., Betts, C., Lakhal, S., & Wood, M. J. A. (2011) · Nature Biotechnology · doi:10.1038/nbt.1807 · Cited by 4,930
Self-citationWatterson, K. R., Bestow, D., Gallagher, J., Hamilton, D. L., Ashford, F. B., Meakin, P. J., & Ashford, M. L. J. (2013) · Neurosignals · doi:10.1159/000334144 · Cited by 3,389
The AMPK signalling pathway coordinates cell growth, autophagy and metabolism
Mihaylova, M. M., & Shaw, R. J. (2011) · Nature Cell Biology · doi:10.1038/ncb2329 · Cited by 2,923
Steinberg, G. R., & Kemp, B. E. (2009) · Physiological Reviews · doi:10.1152/physrev.00011.2008 · Cited by 1,637
Vacuolar ATPases: rotary proton pumps in physiology and pathophysiology
Forgac, M. (2007) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm2272 · Cited by 1,619
Automatic and Quantitative Measurement of Protein-Protein Colocalization in Live Cells
Costes, S. V., Daelemans, D., Cho, E. H., Dobbin, Z., Pavlakis, G., & Lockett, S. (2004) · Biophysical Journal · doi:10.1529/biophysj.103.038422 · Cited by 1,424
Lysosomes and autophagy in cell death control
Kroemer, G., & Jäättelä, M. (2005) · Nature Reviews Cancer · doi:10.1038/nrc1738 · Cited by 1,285
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
Cited by
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
Self-citationMechanisms of neuronal cell death in ischemic stroke and their therapeutic implications
Tuo, Q., Zhang, S., & Lei, P. (2022) · Medicinal Research Reviews · doi:10.1002/med.21817 · Cited by 728
Low-dose metformin targets the lysosomal AMPK pathway through PEN2
Ma, T., Tian, X., Zhang, B., Li, M., Wang, Y., Yang, C., Wu, J., Wei, X., Qu, Q., Yu, Y., et al. (2022) · Nature · doi:10.1038/s41586-022-04431-8 · Cited by 644
Self-citationCrosstalk between metabolism and circadian clocks
Reinke, H., & Asher, G. (2019) · Nature Reviews Molecular Cell Biology · doi:10.1038/s41580-018-0096-9 · Cited by 598
Rabinovitch, R. C., Samborska, B., Faubert, B., Ma, E. H., Gravel, S.-P., Andrzejewski, S., Raissi, T. C., Pause, A., St.-Pierre, J., & Jones, R. G. (2017) · Cell Reports · doi:10.1016/j.celrep.2017.09.026 · Cited by 543
Metadata
- Authors
- Zhang, C.-S., Hawley, S. A., Zong, Y., Li, M., Wang, Z., Gray, A., Ma, T., Cui, J., Feng, J.-W., Zhu, M., Wu, Y.-Q., Li, T. Y., Ye, Z., Lin, S.-Y., Yin, H., Piao, H.-L., Hardie, D. G., & Lin, S.-C.
- Venue
- Nature
- Published
- 2017-07-19
- Volume
- 548
- Issue
- 7665
- Pages
- 112-116
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- OpenAlex
- W2737735431
- Cited by
- 717
- References
- 35
- FWCI
- 22.13
- Type
- journal article
- Language
- en
- Open access
- green
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
How to cite
Cite CoChat for the checks on this page, and the paper for its own findings.
- This page
- CoChat. (2026). Citation check: Fructose-1,6-bisphosphate and aldolase mediate glucose sensing by AMPK. https://app.cochat.ai/papers/10.1038/nature23275
- The paper
- Zhang, C.-S., Hawley, S. A., Zong, Y., Li, M., Wang, Z., Gray, A., Ma, T., Cui, J., Feng, J.-W., Zhu, M., Wu, Y.-Q., Li, T. Y., Ye, Z., Lin, S.-Y., Yin, H., Piao, H.-L., Hardie, D. G., & Lin, S.-C. (2017). Fructose-1,6-bisphosphate and aldolase mediate glucose sensing by AMPK. Nature. https://doi.org/10.1038/nature23275
Data sources
Bibliographic data: Semantic Scholar, OpenAlex, Crossref.
Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.
