PXD079036

PXD079036 is an original dataset announced via ProteomeXchange.

Title	FBP1-mediated Compartmentalization of Glycolytic Enzyme Complexes Suppresses PKM2 Function to Ameliorate MASLD/MASH Progression
Description	Metabolic dysfunction-associated steatotic liver disease (MASLD/MASH) is a progressive hepatic disorder driven primarily by aberrant glycolytic reprogramming in hepatocytes. Fructose-1,6-bisphosphatase 1 (FBP1), a rate-limiting enzyme of gluconeogenesis, is critically involved in diverse metabolic disorders; however, its functional role and regulatory mechanism underlying MASLD/MASH progression remain poorly understood. Pyruvate kinase M2 (PKM2), a key glycolytic enzyme, has emerged as a promising therapeutic target for MASLD/MASH. Here, using clinical specimens, diet-induced murine MASLD/MASH models, and hepatocyte cell lines, we demonstrate consistent downregulation of FBP1 during the transition from MASLD to MASH. Mechanistically, FBP1 directly interacts with PKM2, ENO1, and LDHA to govern the spatial compartmentalization of glycolytic enzyme complexes. FBP1 binding suppresses PKM2 enzymatic activity and restricts excessive hepatic glycolysis, thereby ameliorating intracellular lipid accumulation. Molecular docking and domain mapping further defined the precise binding regions between FBP1 and PKM2, and disruption of their interaction largely abrogated the glycolysis-repressive effects of FBP1. In vivo functional validation confirmed that wild-type FBP1, but not its binding-deficient mutant FBP1 G260R-Δ5, effectively alleviates hepatic steatosis, inflammation, and fibrosis in MASLD/MASH mice. Collectively, this study reveals a previously unrecognized non-canonical function of FBP1 in orchestrating glycolytic complex compartmentalization, establishes a critical molecular crosstalk linking hepatic gluconeogenesis and glycolysis, and provides a novel actionable target for MASLD/MASH therapeutic intervention.
HostingRepository	iProX
AnnounceDate	2026-05-28
AnnouncementXML	Submission_2026-05-28_23:46:57.869.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Busong Wang
SpeciesList	scientific name: Homo sapiens; NCBI TaxID: 9606;
ModificationList	No PTMs are included in the dataset
Instrument	ZenoTOF 7600

Revision	Datetime	Status	ChangeLog Entry
0	2026-05-28 23:46:37	ID requested
⏵ 1	2026-05-28 23:46:58	announced

Dataset with its publication pending

submitter keyword: MASLD, MASH, FBP1, PKM2, glycolysis, hepatic steatosis

Lei Fang
contact affiliation	Nanjing University
contact email	njfanglei@nju.edu.cn
lab head
Busong Wang
contact affiliation	Nanjing University
contact email	602023350041@smail.nju.edu.cn
dataset submitter

iProX dataset URI