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PXD032028-2

PXD032028 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleRequirement of hepatic pyruvate carboxylase during fasting, high fat and ketogenic diet
DescriptionPyruvate has two major fates upon entry into mitochondria, the oxidative decarboxylation to acetyl-CoA or the biotin-dependent carboxylation to oxaloacetate via pyruvate carboxylase (Pcx). Here we have generated mice with a liver specific knockout of pyruvate carboxylase (PcxL-/-) to understand the role of Pcx in hepatic mitochondrial metabolism under disparate physiological states. PcxL-/- mice exhibited a deficit in hepatic gluconeogenesis as expected but were able to maintain systemic euglycemia following a 24hr fast and enhanced ketogenesis. Feeding a high fat diet to PcxL-/- mice resulted in animals that were resistant to glucose intolerance without affecting body weight. However, PcxL-/- mice fed a ketogenic diet for 1 week became severely hypoglycemic, demonstrating a requirement for hepatic Pcx for long term glycemia under carbohydrate limited diets. Loss of Pcx was associated with an induction of protein acetylation in PcxL-/- mice regardless of physiologic state. Furthermore, liver acetyl-proteomics revealed a biased induction in mitochondrial lysine acetylation. These data show that Pcx is important for maintaining the proper balance of pyruvate metabolism between oxidative and anaplerotic pathways.
HostingRepositoryPRIDE
AnnounceDate2023-11-14
AnnouncementXMLSubmission_2023-11-14_08:55:38.964.xml
DigitalObjectIdentifier
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportUnsupported dataset by repository
PrimarySubmitterMichael Wolfgang
SpeciesList scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationListacetylated residue
InstrumentOrbitrap Fusion Lumos
Dataset History
RevisionDatetimeStatusChangeLog Entry
02022-03-03 11:20:35ID requested
12022-10-31 08:28:55announced
22023-11-14 08:55:39announced2023-11-14: Updated project metadata.
Publication List
Dataset with its publication pending
Keyword List
submitter keyword: ketogenesis,acetyl-proteomics, pyruvate carboxylase, mitochondria
Contact List
Michael Wolfgang
contact affiliationDepartments of Biological Chemistry & Pharmacology and Molecular Sciences Johns Hopkins University School of Medicine Baltimore, MD
contact emailmwolfga1@jhmi.edu
lab head
Michael Wolfgang
contact affiliationJohns Hopkins University School of Medicine
contact emailmwolfga1@jhmi.edu
dataset submitter
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