PXD040326

PXD040326 is an original dataset announced via ProteomeXchange.

Dataset Summary

Title	Pyruvate-supported flux through medium chain ketothiolase promotes mitochondrial lipid tolerance in cardiac and skeletal muscles
Description	Even-chain acylcarnitine (AC) metabolites, most of which are generated as byproducts of incomplete fatty acid oxidation (FAO), are viewed as biomarkers of mitochondrial lipid stress attributable to one or more metabolic bottlenecks in the beta-oxidation pathway. The origins and functional implications of FAO bottlenecks remain poorly understood. Here, we combined a sophisticated mitochondrial phenotyping platform with state-of-the-art molecular profiling tools and multiple two-state mouse models of respiratory function to uncover a mechanism that connects AC accumulation to lipid intolerance, metabolic inflexibility, and respiratory inefficiency in skeletal muscle mitochondria. These studies also identified a short chain carbon circuit at the C4 node of FAO wherein reverse flux of glucose-derived acetyl-CoA through medium chain ketothiolase enhances lipid tolerance and redox stability in heart mitochondria by regenerating free CoA and NAD+. The findings help to explain why diminished FAO capacity, AC accumulation, and metabolic inflexibility are tightly linked to poor health outcomes.
HostingRepository	jPOST
AnnounceDate	2023-04-14
AnnouncementXML	Submission_2023-04-14_07:54:19.415.xml
DigitalObjectIdentifier
ReviewLevel	Non peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Paul Grimsrud
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	S-carboxamidomethyl-L-cysteine; L-methionine sulfoxide
Instrument	Q Exactive

Dataset History

Revision	Datetime	Status	ChangeLog Entry
0	2023-02-22 06:39:28	ID requested
⏵ 1	2023-04-14 07:54:19	announced

Publication List

Dataset with its publication pending

Dataset with its publication pending

Keyword List

submitter keyword: mitochondria, label-free proteomics, heart, skeletal muscle, fatty acid oxidation

submitter keyword: mitochondria, label-free proteomics, heart, skeletal muscle, fatty acid oxidation

Contact List

Deborah M. Muoio
lab head
Paul Grimsrud
contact affiliation	Duke University
dataset submitter

Full Dataset Link List

jPOST dataset URI
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jPOST dataset URI

Dataset FTP location
NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.jpostdb.org/JPST002051/