PXD058152-1

PXD058152 is an original dataset announced via ProteomeXchange.

Dataset Summary

Title	Mitochondrial Calcium Signaling Regulates Branched-Chain Amino Acid Catabolism in Fibrolamellar Carcinoma
Description	Metabolic adaptations in response to changes in energy supply and demand are essential for survival. The mitochondrial calcium uniporter plays a key role in coordinating metabolic homeostasis by regulating TCA cycle activation, mitochondrial fatty acid oxidation and cellular calcium signaling. However, a comprehensive analysis of uniporter-regulated mitochondrial metabolic pathways has remained unexplored. Here, we investigate metabolic consequences of uniporter loss- and gain-of-function using uniporter knock out cells and the liver cancer fibrolamellar carcinoma (FLC), which we demonstrate to have elevated mitochondrial calcium levels. Our results reveal that branched chain amino acid (BCAA) catabolism and the urea cycle are uniporter-regulated metabolic pathways. Reduced uniproter function increases expression of BCAA catabolism genes, and the urea cycle enzyme ornithine transcarbamylase (OTC). In contrast, high uniporter activity in FLC suppresses their expression. This suppression happens via the transcription factor KLF15, a master regulator of liver metabolism, suggesting that calcium signaling plays a central role in FLC-associated metabolic changes, including hyperammonemia. Consistent with this, activation of BCAA catabolism in FLC cells impairs their growth. Collectively, our study identifies an important role for mitochondrial calcium signaling in metabolic adaptation through transcriptional regulation of metabolism and elucidates its importance for BCAA and ammonia metabolism in FLC.
HostingRepository	MassIVE
AnnounceDate	2024-11-21
AnnouncementXML	Submission_2024-11-21_14:35:13.521.xml
DigitalObjectIdentifier
ReviewLevel	Non peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Shao-En Ong
SpeciesList	scientific name: Homo sapiens; common name: human; NCBI TaxID: 9606;
ModificationList	No PTMs are included in the dataset
Instrument	Orbitrap Fusion Lumos

Dataset History

Revision	Datetime	Status	ChangeLog Entry
0	2024-11-21 14:19:42	ID requested
⏵ 1	2024-11-21 14:35:13	announced

Publication List

no publication

no publication

Keyword List

submitter keyword: MCU, DatasetType:Proteomics

submitter keyword: MCU, DatasetType:Proteomics

Contact List

Yasemin Sancak
contact affiliation	University of Washington
contact email	sancak@uw.edu
lab head
Shao-En Ong
contact affiliation	University of Washington
contact email	shaoen@uw.edu
dataset submitter

Full Dataset Link List

MassIVE dataset URI
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MassIVE 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://massive.ucsd.edu/v07/MSV000096493/