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PXD081706-1

PXD081706 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleProhibitin Controls MRS2-Mediated Mitochondrial Mg2+ Uptake to Shape Bioenergetics
DescriptionMitochondrial magnesium (mMg2+) is essential for cellular metabolism and bioenergetics, yet the mechanisms governing its transport remain poorly understood. Although MRS2 constitutes the pore of the mMg2+ channel, the molecular machinery regulating its function is unknown. Here, unbiased proteomics identified the prohibitin (PHB) complex as a prominent MRS2-interacting partner. Integrated biochemical and functional analyses demonstrate that the conserved coiled-coil domain mediates MRS2 homo-oligomerization, whereas the C-terminal region of MRS2 interacts with PHB1 to promote channel activity. Quantitative calibration of mitochondria-targeted MagFRET sensors revealed maximal mMg2+ uptake (appx. 15 mM), which was markedly reduced in Phb1-deficient hepatocytes. Complementary loss- and gain-of-function studies establish PHB1 as a positive regulator of MRS2-mediated mMg2+ uptake without affecting MCU-dependent Ca2+ transport. In vivo, hepatic Phb1 deletion attenuated mMg2+ uptake and enhanced cellular bioenergetics. These findings identify PHB1 as an activator of the MRS2, advancing our understanding of mMg2+ uptake machinery and its role in metabolic regulation.
HostingRepositoryMassIVE
AnnounceDate2026-07-27
AnnouncementXMLSubmission_2026-07-27_07:07:30.026.xml
DigitalObjectIdentifier
ReviewLevelNon peer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportSupported dataset by repository
PrimarySubmitterSusan T. Weintraub
SpeciesList scientific name: Homo sapiens; common name: human; NCBI TaxID: 9606;
ModificationListCarbamidomethyl; Oxidation; Deamidated
InstrumentLTQ Orbitrap Velos Pro
Dataset History
RevisionDatetimeStatusChangeLog Entry
02026-07-27 07:00:20ID requested
12026-07-27 07:07:30announced
Publication List
no publication
Keyword List
submitter keyword: Magnesium, LC-tandem mass spectrometry, Mitochondria, MRS2, PHB1, DatasetType:Proteomics
Contact List
Madesh Muniswamy, M.S., Ph.D.
contact affiliationUniversity of Texas Health Science Center at San Antonio
contact emailmuniswamy@uthscsa.edu
lab head
Susan T. Weintraub
contact affiliationUT Health Science Center San Antonio
contact emailweintraub@uthscsa.edu
dataset submitter
Full Dataset Link List
MassIVE dataset URI
Dataset FTP location
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