PXD057017-1

PXD057017 is an original dataset announced via ProteomeXchange.

Title	Pantothenate kinase 4 controls skeletal muscle substrate metabolism
Description	Metabolic flexibility in skeletal muscle is essential for maintaining healthy glucose and lipid metabolism, and its dysfunction is closely linked to metabolic diseases. Exercise enhances metabolic flexibility, making it an important tool for discovering mechanisms that promote efficient energy metabolism. We herein discover pantothenate kinase 4 (PanK4) as a conserved exercise target with high abundance in muscle. Germline deletion of Pank4 reduces circulating IGF-1 and stunts growth in mice. Muscle-specific deletion of Pank4 leads to a reduction in carnitzed and in impaired fatty acid oxidation in oxidative muscle which is related to higher acetyl-CoA and malonyl levels. Acetyl-CoA levels were persistently elevated in SkM lacking PanK4, independent of prandial state. In addition to perturbations of fatty acid oxidation, high SkM acetyl-CoA levels were associated with whole-body glucose intolerance, impaired insulin-stimulated glucose uptake into glycolytic SkM and impaired SkM glucose uptake during exercise. Conversely, we show that an increase in PanK4 lowers acetyl-CoA and increases glucose uptake in glycolytic SkM. Our findings identify PanK4 as a conserved exercise target that regulates SkM acetyl-CoA levels and plays a key role in lipid and glucose metabolism.
HostingRepository	PRIDE
AnnounceDate	2024-10-25
AnnouncementXML	Submission_2024-10-24_23:25:30.762.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Stefanie Hauck
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	phosphorylated residue; monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Q Exactive HF

Revision	Datetime	Status	ChangeLog Entry
0	2024-10-21 07:50:13	ID requested
⏵ 1	2024-10-24 23:25:31	announced

Dataset with its publication pending

submitter keyword: pantothenate kinase 4 (PanK4), lipid and glucose metabolism,Skeletal muscle

Stefanie M. Hauck
contact affiliation	Research Unit Protein Science, Helmholtz Center Munich, Neuherberg, Germany
contact email	hauck@helmholtz-muenchen.de
lab head
Stefanie Hauck
contact affiliation	Research Unit Protein Science, Helmholtz Zentrum München
contact email	hauck@helmholtz-muenchen.de
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD057017
     1. Label: PRIDE project
     2. Name: Pantothenate kinase 4 controls skeletal muscle substrate metabolism