PXD008766 is an
original dataset announced via ProteomeXchange.
Dataset Summary
Title | Hepatic mitochondrial proteome dynamics in NAFLD mice |
Description | Nonalcoholic 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. |
HostingRepository | PRIDE |
AnnounceDate | 2024-10-22 |
AnnouncementXML | Submission_2024-10-22_04:04:39.398.xml |
DigitalObjectIdentifier | |
ReviewLevel | Peer-reviewed dataset |
DatasetOrigin | Original dataset |
RepositorySupport | Unsupported dataset by repository |
PrimarySubmitter | Kwangwon Lee |
SpeciesList | scientific name: Mus musculus (Mouse); NCBI TaxID: 10090; |
ModificationList | monohydroxylated residue; acetylated residue; iodoacetamide derivatized residue |
Instrument | Q Exactive |
Dataset History
Revision | Datetime | Status | ChangeLog Entry |
0 | 2018-01-26 06:59:03 | ID requested | |
1 | 2018-11-21 05:40:36 | announced | |
2 | 2019-02-26 07:58:26 | announced | Updated publication reference for PubMed record(s): 30171159. |
⏵ 3 | 2024-10-22 04:04:47 | announced | 2024-10-22: 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 affiliation | NEOMED |
contact email | tkasumov@neomed.edu |
lab head | |
Kwangwon Lee |
contact affiliation | NEOMED |
contact email | klee6@neomed.edu |
dataset submitter | |
Full Dataset Link List
Dataset FTP location
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PRIDE project URI |
Repository Record List
[ + ]
[ - ]
- PRIDE
- PXD008766
- Label: PRIDE project
- Name: Hepatic mitochondrial proteome dynamics in NAFLD mice