PXD008766

PXD008766 is an original dataset announced via ProteomeXchange.

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

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.

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]

curator keyword: Biological

submitter keyword: oxidative phosphorylation, proteome dynamics,NAFLD, mitochondrial dysfunction, heavy water metabolic labeling, oxidative stress, energy metabolism, turnover, LC-MS/MS

Takhar Kasumov
contact affiliation	NEOMED
contact email	tkasumov@neomed.edu
lab head
Kwangwon Lee
contact affiliation	NEOMED
contact email	klee6@neomed.edu
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD008766
     1. Label: PRIDE project
     2. Name: Hepatic mitochondrial proteome dynamics in NAFLD mice