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PXD035968

PXD035968 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleThe aldolase inhibitor aldometanib mimics glucose starvation to activate lysosomal AMPK
DescriptionThe activity of 5’-adenosine monophosphate-activated protein kinase (AMPK) is inversely correlated with the cellular availability of glucose. When glucose levels are low, the glycolytic enzyme aldolase is not bound to fructose-1,6-bisphosphate (FBP) and, instead, signals to activate lysosomal AMPK. Here, we have screened for inhibitors that prevent FBP from binding to aldolase, and have identified Aldometanib that prevents FBP from binding to v-ATPase-associated aldolase and activates lysosomal AMPK, thereby mimicking a cellular state of glucose starvation. In male mice, Aldometanib elicits an insulin-independent glucose lowering effect, without causing hypoglycaemia. Aldometanib also alleviates fatty liver and nonalcoholic steatohepatitis (NASH) in obese male rodents. Moreover, Aldometanib extends lifespan and healthspan in both Caenorhabditis elegans and mice. Taken together, Aldometanib mimics and adopts the lysosomal AMPK activation pathway associated with glucose starvation to exert physiological roles, and might have potential as a therapeutic for metabolic disorders in humans.
HostingRepositoryiProX
AnnounceDate2022-08-10
AnnouncementXMLSubmission_2022-10-12_01:10:51.890.xml
DigitalObjectIdentifier
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportUnsupported dataset by repository
PrimarySubmitterChensong Zhang
SpeciesList scientific name: Oryctolagus cuniculus; NCBI TaxID: 9986;
ModificationListNo PTMs are included in the dataset
InstrumenttimsTOF Pro
Dataset History
RevisionDatetimeStatusChangeLog Entry
02022-08-10 19:40:03ID requested
12022-08-10 19:40:17announced
22022-10-12 01:10:52announced2022-10-12: Update publication information.
Publication List
Zhang CS, Li M, Wang Y, Li X, Zong Y, Long S, Zhang M, Feng JW, Wei X, Liu YH, Zhang B, Wu J, Zhang C, Lian W, Ma T, Tian X, Qu Q, Yu Y, Xiong J, Liu DT, Wu Z, Zhu M, Xie C, Wu Y, Xu Z, Yang C, Chen J, Huang G, He Q, Huang X, Zhang L, Sun X, Liu Q, Ghafoor A, Gui F, Zheng K, Wang W, Wang ZC, Yu Y, Zhao Q, Lin SY, Wang ZX, Piao HL, Deng X, Lin SC, The aldolase inhibitor aldometanib mimics glucose starvation to activate lysosomal AMPK. Nat Metab, 4(10):1369-1401(2022) [pubmed]
Keyword List
submitter keyword: aldometanib, aldolase inhibitor, AMPK, lysosomal pathway
Contact List
Shengcai Lin
contact affiliationXiamen University
contact emaillinsc@xmu.edu.xn
lab head
Chensong Zhang
contact affiliationXiamen University
contact emailcszhang@xmu.edu.cn
dataset submitter
Full Dataset Link List
iProX dataset URI