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PXD067549-1

PXD067549 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleHepatocyte mitochondrial NAD+ content is limiting for liver regeneration
DescriptionSupplemental NAD+ precursors show metabolic and functional benefits in rodent models of disease and are being explored as potential therapeutics in human studies. However, the wide range of processes that involve NAD+ in every cell and subcellular compartment make it difficult to narrow down mechanisms of action. Here we provide evidence that for a well-established benefit of NAD+ precursors in mice, faster liver regeneration, nearly the entire effect can be attributed to the concentration of NAD+ in hepatocyte mitochondria. We find that mitochondrial NAD+ concentration in hepatocytes of male mice is determined by the expression of the transporter SLC25A51 (MCART1), as has previously been shown in cultured cells. Heterozygous loss of SLC25A51 modestly decreases mitochondrial NAD+ content in multiple tissues and impairs liver regeneration, while hepatocyte-specific overexpression is sufficient to enhance regeneration comparably to the effect of systemic supplements, despite increasing NAD+ only in mitochondria. Thus, the hepatocyte mitochondrial NAD+ pool is a key determinant of the rate of liver regeneration.
HostingRepositoryPRIDE
AnnounceDate2025-11-06
AnnouncementXMLSubmission_2025-11-05_18:04:33.330.xml
DigitalObjectIdentifier
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportUnsupported dataset by repository
PrimarySubmitterKevin A Janssen
SpeciesList scientific name: Mus musculus (Mouse); NCBI TaxID: NEWT:10090;
ModificationListiodoacetamide derivatized residue
InstrumentQ Exactive HF
Dataset History
RevisionDatetimeStatusChangeLog Entry
02025-08-21 05:12:27ID requested
12025-11-05 18:04:33announced
Publication List
10.1038/S42255-025-01408-5;
Keyword List
submitter keyword: Mitochondria,Mouse, Liver, LC-MS/MS
Contact List
Douglas Wallace
contact affiliationCenter for Mitochondrial and Epigenomic Medicine, Children's Hospital of Philadelphia, Philadelphia, PA, USA
contact emailwallaced1@chop.edu
lab head
Kevin A Janssen
contact affiliationChildren's Hospital of Philadelphia
contact emailkxjanssen@gmail.com
dataset submitter
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Dataset FTP location
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