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PXD008766

PXD008766 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleHepatic mitochondrial proteome dynamics in NAFLD mice
DescriptionNonalcoholic fatty liver disease (NAFLD) is associated with hepatic mitochondrial dysfunction characterized by reduced ATP synthesis. We applied the 2H2O-metabolic labeling approach to test the hypothesis that the reduced stability of oxidative phosphorylation proteins contributes to mitochondrial dysfunction in a diet-induced mouse model of NAFLD. A high fat diet containing cholesterol (a so-called Western diet (WD)) led to hepatic oxidative stress, steatosis, inflammation and mild fibrosis, all markers of NAFLD, in LDLR-/- mice. In addition, compared to controls, livers from NAFLD mice had reduced citrate synthase activity and ATP content, suggesting reduced mitochondrial oxidative capacity. Proteome dynamics analysis revealed that mitochondrial dysfunction is associated with reduced average half-lives of mitochondrial proteins in NAFLD mice (5.41±0.46 vs. 5.15±0.49 day, P<0.05). In particular, the WD reduced stability of oxidative phosphorylation subunits, including cytochrome c oxidase subunit 4 isoform 1 of complex III (5.9 ± 0.1 vs 3.4 ± 0.8 day), ATP synthase subunit α (6.3±0.4 vs. 5.5±0.4 day) and ATP synthase F(0) complex subunit B1 of complex V (8.5±0.6 vs. 6.5±0.2 day) (P<0.05). These changes were associated with impaired complex III and F0F1-ATP synthase activities, suggesting that increased degradation of mitochondrial proteins contributed to hepatic mitochondrial dysfunction in NAFLD mice. Autophagy, but not proteasomal degradation, contributed to increased clearance of hepatic mitochondrial proteins in NAFLD mice. In conclusion, the proteome dynamics approach suggests that alterations in mitochondrial proteome dynamics is involved in hepatic mitochondrial dysfunction in NAFLD.
HostingRepositoryPRIDE
AnnounceDate2024-10-22
AnnouncementXMLSubmission_2024-10-22_04:04:39.398.xml
DigitalObjectIdentifier
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportUnsupported dataset by repository
PrimarySubmitterKwangwon Lee
SpeciesList scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationListmonohydroxylated residue; acetylated residue; iodoacetamide derivatized residue
InstrumentQ Exactive
Dataset History
RevisionDatetimeStatusChangeLog Entry
02018-01-26 06:59:03ID requested
12018-11-21 05:40:36announced
22019-02-26 07:58:26announcedUpdated publication reference for PubMed record(s): 30171159.
32024-10-22 04:04:47announced2024-10-22: Updated project metadata.
Publication List
10.1074/mcp.ra118.000961;
Lee K, Haddad A, Osme A, Kim C, Borzou A, Ilchenko S, Allende D, Dasarathy S, McCullough A, Sadygov RG, Kasumov T, Hepatic Mitochondrial Defects in a Nonalcoholic Fatty Liver Disease Mouse Model Are Associated with Increased Degradation of Oxidative Phosphorylation Subunits. Mol Cell Proteomics, 17(12):2371-2386(2018) [pubmed]
Keyword List
curator keyword: Biological
submitter keyword: oxidative phosphorylation, proteome dynamics,NAFLD, mitochondrial dysfunction, heavy water metabolic labeling, oxidative stress, energy metabolism, turnover, LC-MS/MS
Contact List
Takhar Kasumov
contact affiliationNEOMED
contact emailtkasumov@neomed.edu
lab head
Kwangwon Lee
contact affiliationNEOMED
contact emailklee6@neomed.edu
dataset submitter
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Dataset FTP location
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PRIDE project URI
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