Core C will provide a state of the art proteomics core to improve the understanding of the molecular changes in the mitochondria associated with reactive oxygen species (ROS) and aging. The four research projects seek to understand the role of mitochondrial catalase and mimetics on health and lifespan in mouse models. Integral to the success of the program project grant is the measurement of changes in relative mitochondrial protein abundance and half-life in health, disease, and aging. To support the needs of the individual research projects, the Proteomics Core has three specific aims: 1)to perform perform the unbiased detection of differences in peptide/protein abundance between complex mixtures. To understand the effect of ROS on mitochondrial function we will provide the capability to comprehensively detect differences in A) protein abundance between mitochondrial enriched fractions and B) peptide abundance between samples following enrichment of peptides with oxidative modifications. 2) to perform targeted analysis of protein abundance for mitochondrial proteins of interest. 3) to perform global measurement of individual mitochondrial protein halflife. An active area of technology development within the core will be refining the capability for the measurement of individual protein half-life in a rodent system. We have the capability to measure mitochondrial protein half-life for hundreds of proteins in a single measurement.

Public Health Relevance

Understanding the changes that take place in the proteins (proteome) of treated and untreated mitochondria in aging tissues contributes to fundamental insights and understandings of the health benefits that we intend to achieve in the Program Project studies.

Agency
National Institute of Health (NIH)
Institute
National Institute on Aging (NIA)
Type
Research Program Projects (P01)
Project #
5P01AG001751-31
Application #
8643179
Study Section
Special Emphasis Panel (ZAG1-ZIJ-6)
Project Start
Project End
Budget Start
2014-03-01
Budget End
2015-02-28
Support Year
31
Fiscal Year
2014
Total Cost
$201,442
Indirect Cost
$71,058
Name
University of Washington
Department
Type
DUNS #
605799469
City
Seattle
State
WA
Country
United States
Zip Code
98195
Basisty, Nathan B; Liu, Yuxin; Reynolds, Jason et al. (2018) Stable Isotope Labeling Reveals Novel Insights Into Ubiquitin-Mediated Protein Aggregation With Age, Calorie Restriction, and Rapamycin Treatment. J Gerontol A Biol Sci Med Sci 73:561-570
Kramer, Philip A; Duan, Jicheng; Gaffrey, Matthew J et al. (2018) Fatiguing contractions increase protein S-glutathionylation occupancy in mouse skeletal muscle. Redox Biol 17:367-376
Zhang, Huiliang; Gong, Guohua; Wang, Pei et al. (2018) Heart specific knockout of Ndufs4 ameliorates ischemia reperfusion injury. J Mol Cell Cardiol 123:38-45
Ge, Xuan; Ciol, Marcia A; Pettan-Brewer, Christina et al. (2017) Self-motivated and stress-response performance assays in mice are age-dependent. Exp Gerontol 91:1-4
Sweetwyne, Mariya T; Pippin, Jeffrey W; Eng, Diana G et al. (2017) The mitochondrial-targeted peptide, SS-31, improves glomerular architecture in mice of advanced age. Kidney Int 91:1126-1145
Liu, Sophia Z; Marcinek, David J (2017) Skeletal muscle bioenergetics in aging and heart failure. Heart Fail Rev 22:167-178
Basisty, Nathan; Dai, Dao-Fu; Gagnidze, Arni et al. (2016) Mitochondrial-targeted catalase is good for the old mouse proteome, but not for the young: 'reverse' antagonistic pleiotropy? Aging Cell 15:634-45
Treuting, P M; Snyder, J M; Ikeno, Y et al. (2016) The Vital Role of Pathology in Improving Reproducibility and Translational Relevance of Aging Studies in Rodents. Vet Pathol 53:244-9
Ahn, Eun Hyun; Lee, Seung Hyuk; Kim, Joon Yup et al. (2016) Decreased Mitochondrial Mutagenesis during Transformation of Human Breast Stem Cells into Tumorigenic Cells. Cancer Res 76:4569-78
Kruse, Shane E; Karunadharma, Pabalu P; Basisty, Nathan et al. (2016) Age modifies respiratory complex I and protein homeostasis in a muscle type-specific manner. Aging Cell 15:89-99

Showing the most recent 10 out of 285 publications