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40
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Text
A resource consisting primarily of words for reading. Examples include books, letters, dissertations, poems, newspapers, articles, archives of mailing lists. Note that facsimiles or images of texts are still of the genre Text.
URL Address
<a href="http://doi.org/10.1074/mcp.RA118.000961" target="_blank" rel="noreferrer noopener">http://doi.org/10.1074/mcp.RA118.000961</a>
Pages
2371–2386
Issue
12
Volume
17
Dublin Core
The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/.
Title
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Hepatic Mitochondrial Defects in a Nonalcoholic Fatty Liver Disease Mouse Model Are Associated with Increased Degradation of Oxidative Phosphorylation Subunits.
Publisher
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Molecular & cellular proteomics : MCP
Date
A point or period of time associated with an event in the lifecycle of the resource
2018
2018-12
Subject
The topic of the resource
Energy metabolism; heavy water; Mass Spectrometry; metabolic labeling; Mitochondria function or biology; oxidative phosphorylation; Oxidative stress; Protein Degradation; Protein Turnover
Creator
An entity primarily responsible for making the resource
Lee Kwangwon; Haddad Andrew; Osme Abdullah; Kim Chunki; Borzou Ahmad; Ilchenko Sergei; Allende Daniela; Dasarathy Srinivasan; McCullough Arthur; Sadygov Rovshan G; Kasumov Takhar
Description
An account of the resource
Nonalcoholic fatty liver disease (NAFLD) is associated with hepatic mitochondrial dysfunction characterized by reduced ATP synthesis. We applied the (2)H2O-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 low density cholesterol (LDL) receptor deficient (LDLR(-/-)) mice. In addition, compared with controls (LDLR(-/-) mice on normal diet), livers from NAFLD mice had reduced citrate synthase activity and ATP content, suggesting mitochondrial impairment. Proteome dynamics study revealed that mitochondrial defects are associated with reduced average half-lives of mitochondrial proteins in NAFLD mice (5.41 +/- 0.46 versus 5.15 +/- 0.49 day, p \textless 0.05). In particular, the WD reduced stability of oxidative phosphorylation subunits, including cytochrome b-c1 complex subunit 1 (5.9 +/- 0.1 versus 3.4 +/- 0.8 day), ATP synthase subunit alpha (6.3 +/- 0.4 versus 5.5 +/- 0.4 day) and ATP synthase F(0) complex subunit B1 of complex V (8.5 +/- 0.6 versus 6.5 +/- 0.2 day) (p \textless 0.05). These changes were associated with impaired complex III and F0F1-ATP synthase activities. Markers of mitophagy were increased, but proteasomal degradation activity were reduced in NAFLD mice liver, suggesting that ATP deficiency because of reduced stability of oxidative phosphorylation complex subunits contributed to inhibition of ubiquitin-proteasome and activation of mitophagy. In conclusion, the (2)H2O-metabolic labeling approach shows that increased degradation of hepatic oxidative phosphorylation subunits contributed to mitochondrial impairment in NAFLD mice.
Identifier
An unambiguous reference to the resource within a given context
<a href="http://doi.org/10.1074/mcp.RA118.000961" target="_blank" rel="noreferrer noopener">10.1074/mcp.RA118.000961</a>
Rights
Information about rights held in and over the resource
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
2018
Allende Daniela
Borzou Ahmad
Dasarathy Srinivasan
Department of Pharmaceutical Sciences
Energy Metabolism
Haddad Andrew
Heavy water
Ilchenko Sergei
Kasumov Takhar
Kim Chunki
Lee Kwangwon
Mass spectrometry
McCullough Arthur
metabolic labeling
Mitochondria function or biology
Molecular & cellular proteomics : MCP
NEOMED College of Pharmacy
Osme Abdullah
oxidative phosphorylation
Oxidative Stress
Protein Degradation
Protein Turnover
Sadygov Rovshan G
-
Text
A resource consisting primarily of words for reading. Examples include books, letters, dissertations, poems, newspapers, articles, archives of mailing lists. Note that facsimiles or images of texts are still of the genre Text.
URL Address
<a href="http://doi.org/10.1021/acs.jproteome.8b00417" target="_blank" rel="noreferrer noopener">http://doi.org/10.1021/acs.jproteome.8b00417</a>
Pages
3740–3748
Issue
11
Volume
17
Dublin Core
The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/.
Title
A name given to the resource
d2ome, Software for in Vivo Protein Turnover Analysis Using Heavy Water Labeling and LC-MS, Reveals Alterations of Hepatic Proteome Dynamics in a Mouse Model of NAFLD.
Publisher
An entity responsible for making the resource available
Journal of proteome research
Date
A point or period of time associated with an event in the lifecycle of the resource
2018
2018-11
Subject
The topic of the resource
40S ribosomal proteins; in vivo protein turnover; isotopomer quantification; metabolic labeling; NAFLD; nonlinear least-squares modeling; peak detection and integration; protein half-life; proteome dynamics; UPR
Creator
An entity primarily responsible for making the resource
Sadygov Rovshan G; Avva Jayant; Rahman Mahbubur; Lee Kwangwon; Ilchenko Sergei; Kasumov Takhar; Borzou Ahmad
Description
An account of the resource
Metabolic labeling with heavy water followed by LC-MS is a high throughput approach to study proteostasis in vivo. Advances in mass spectrometry and sample processing have allowed consistent detection of thousands of proteins at multiple time points. However, freely available automated bioinformatics tools to analyze and extract protein decay rate constants are lacking. Here, we describe d2ome-a robust, automated software solution for in vivo protein turnover analysis. d2ome is highly scalable, uses innovative approaches to nonlinear fitting, implements Grubbs' outlier detection and removal, uses weighted-averaging of replicates, applies a data dependent elution time windowing, and uses mass accuracy in peak detection. Here, we discuss the application of d2ome in a comparative study of protein turnover in the livers of normal vs Western diet-fed LDLR(-/-) mice (mouse model of nonalcoholic fatty liver disease), which contained 256 LC-MS experiments. The study revealed reduced stability of 40S ribosomal protein subunits in the Western diet-fed mice.
Identifier
An unambiguous reference to the resource within a given context
<a href="http://doi.org/10.1021/acs.jproteome.8b00417" target="_blank" rel="noreferrer noopener">10.1021/acs.jproteome.8b00417</a>
Rights
Information about rights held in and over the resource
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
2018
40S ribosomal proteins
Avva Jayant
Borzou Ahmad
Department of Pharmaceutical Sciences
Ilchenko Sergei
in vivo protein turnover
isotopomer quantification
Journal of proteome research
Kasumov Takhar
Lee Kwangwon
metabolic labeling
NAFLD
NEOMED College of Pharmacy
nonlinear least-squares modeling
peak detection and integration
protein half-life
Proteome dynamics
Rahman Mahbubur
Sadygov Rovshan G
UPR