PXD050130

PXD050130 is an original dataset announced via ProteomeXchange.

Title	Transketolase promotes MAFLD by limiting inosine-induced mitochondrial activity (Proteomics)
Description	Metabolic dysfunction-associated fatty liver disease (MAFLD) has a global prevalence of about 25% and no approved therapy. Using metabolomic and proteomic analyses, we identified high expression of hepatic transketolase (TKT), a metabolic enzyme of the pentose phosphate pathway, in human and mouse MAFLD. Hyperinsulinemia promoted TKT expression through the insulin receptor-CCAAT/enhancer-binding protein alpha axis. Utilizing liver-specific TKT overexpression and knockout mouse models, we demonstrated that TKT was sufficient and required for MAFLD progression. Further metabolic flux analysis revealed that Tkt deletion increased hepatic inosine levels to activate the protein kinase A-cAMP response element binding protein cascade, promote phosphatidylcholine synthesis and improve mitochondrial function. Moreover, insulin induced hepatic TKT to limit inosine-dependent mitochondrial activity. Importantly, N-acetylgalactosamine (GalNAc)-siRNA conjugates targeting hepatic TKT showed promising therapeutic effects on mouse MAFLD. Our study uncovers how hyperinsulinemia regulates TKT-orchestrated inosine metabolism and mitochondrial function, and provides a novel therapeutic strategy for MAFLD prevention and treatment.
HostingRepository	iProX
AnnounceDate	2024-02-26
AnnouncementXML	Submission_2024-03-31_22:53:35.533.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Lingfeng Tong
SpeciesList	scientific name: Homo sapiens; NCBI TaxID: 9606;
ModificationList	No PTMs are included in the dataset
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2024-02-25 23:08:31	ID requested
⏵ 1	2024-03-31 22:53:36	announced

Tong L, Chen Z, Li Y, Wang X, Yang C, Li Y, Zhu Y, Lu Y, Liu Q, Xu N, Shao S, Wu L, Zhang P, Wu G, Wu X, Chen X, Fang J, Jia R, Xu T, Li B, Zheng L, Liu J, Tong X, Transketolase promotes MAFLD by limiting inosine-induced mitochondrial activity. Cell Metab, ():(2024) [pubmed]

submitter keyword: Metabolic dysfunction-associated fatty liver disease (MAFLD), transketolase, mitochondrial function, inosine, GalNAc-siRNA conjugates

Xuemei Tong
contact affiliation	Shanghai Jiao Tong University School of Medicine
contact email	xuemeitong@shsmu.edu.cn
lab head
Lingfeng Tong
contact affiliation	Shanghai Jiaotong University School of Medicine
contact email	lingfeng_tong@163.com
dataset submitter

iProX dataset URI