PXD032028-2

PXD032028 is an original dataset announced via ProteomeXchange.

Title	Requirement of hepatic pyruvate carboxylase during fasting, high fat and ketogenic diet
Description	Pyruvate 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.
HostingRepository	PRIDE
AnnounceDate	2023-11-14
AnnouncementXML	Submission_2023-11-14_08:55:38.964.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Michael Wolfgang
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	acetylated residue
Instrument	Orbitrap Fusion Lumos

Revision	Datetime	Status	ChangeLog Entry
0	2022-03-03 11:20:35	ID requested
1	2022-10-31 08:28:55	announced
⏵ 2	2023-11-14 08:55:39	announced	2023-11-14: Updated project metadata.

Dataset with its publication pending

submitter keyword: ketogenesis,acetyl-proteomics, pyruvate carboxylase, mitochondria

Michael Wolfgang
contact affiliation	Departments of Biological Chemistry & Pharmacology and Molecular Sciences Johns Hopkins University School of Medicine Baltimore, MD
contact email	mwolfga1@jhmi.edu
lab head
Michael Wolfgang
contact affiliation	Johns Hopkins University School of Medicine
contact email	mwolfga1@jhmi.edu
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD032028
     1. Label: PRIDE project
     2. Name: Requirement of hepatic pyruvate carboxylase during fasting, high fat and ketogenic diet