PXD035968
PXD035968 is an original dataset announced via ProteomeXchange.
Dataset Summary
Title | The aldolase inhibitor aldometanib mimics glucose starvation to activate lysosomal AMPK |
Description | The 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. |
HostingRepository | iProX |
AnnounceDate | 2022-08-10 |
AnnouncementXML | Submission_2022-10-12_01:10:51.890.xml |
DigitalObjectIdentifier | |
ReviewLevel | Peer-reviewed dataset |
DatasetOrigin | Original dataset |
RepositorySupport | Unsupported dataset by repository |
PrimarySubmitter | Chensong Zhang |
SpeciesList | scientific name: Oryctolagus cuniculus; NCBI TaxID: 9986; |
ModificationList | No PTMs are included in the dataset |
Instrument | timsTOF Pro |
Dataset History
Revision | Datetime | Status | ChangeLog Entry |
---|---|---|---|
0 | 2022-08-10 19:40:03 | ID requested | |
1 | 2022-08-10 19:40:17 | announced | |
⏵ 2 | 2022-10-12 01:10:52 | announced | 2022-10-12: 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 affiliation | Xiamen University |
contact email | linsc@xmu.edu.xn |
lab head | |
Chensong Zhang | |
contact affiliation | Xiamen University |
contact email | cszhang@xmu.edu.cn |
dataset submitter |
Full Dataset Link List
iProX dataset URI |