Abstract

Tthe role of perturbations in mitochondrial biogenesis in the development and progression of complications of diabetes in the heart and skeletal is being explored using both cellular models and genetically modified mouse models. Candidate proteins identified that may modulate the mitochondrial biogenesis program in diabetes have been identified and these are being characterized via functional genomics to evaluate their role in the development of mitochondrial dysfunction in diabetes. The proteins that are being investigated modulate mitochondrial biology via the modification of lysine residues of mitochondrial proteins the target regulatory proteins modulating these post-translational modifications being explored include acetyl-transferases, deacetylases and ubiquitin ligases. Translational studies are being performed to evaluate whether these experimental findings are valid in the human condition.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Investigator-Initiated Intramural Research Projects (ZIA)
Project #
1ZIAHL005199-03
Application #
7969124
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
3
Fiscal Year
2009
Total Cost
$1,478,809
Indirect Cost

  Institution

Name
National Heart, Lung, and Blood Institute
Department
Type
DUNS #
City
State
Country
Zip Code

  Publications

Han, Kim; Nguyen, An; Traba, Javier et al. (2018) A Pilot Study To Investigate the Immune-Modulatory Effects of Fasting in Steroid-Naive Mild Asthmatics. J Immunol 201:1382-1388
Thapa, Dharendra; Wu, Kaiyuan; Stoner, Michael W et al. (2018) The protein acetylase GCN5L1 modulates hepatic fatty acid oxidation activity via acetylation of the mitochondrial ?-oxidation enzyme HADHA. J Biol Chem 293:17676-17684
Scott, Iain; Wang, Lingdi; Wu, Kaiyuan et al. (2018) GCN5L1/BLOS1 Links Acetylation, Organelle Remodeling, and Metabolism. Trends Cell Biol 28:346-355
Akkaya, Munir; Traba, Javier; Roesler, Alexander S et al. (2018) Second signals rescue B cells from activation-induced mitochondrial dysfunction and death. Nat Immunol 19:871-884
Wang, Hongsheng; Gonzalez-Garcia, Ines; Traba, Javier et al. (2017) ATP-degrading ENPP1 is required for survival (or persistence) of long-lived plasma cells. Sci Rep 7:17867
Han, Kim; Hassanzadeh, Shahin; Singh, Komudi et al. (2017) Parkin regulation of CHOP modulates susceptibility to cardiac endoplasmic reticulum stress. Sci Rep 7:2093
Webster, Bradley R; Scott, Iain; Traba, Javier et al. (2014) Regulation of autophagy and mitophagy by nutrient availability and acetylation. Biochim Biophys Acta 1841:525-34
Sack, Michael N (2013) Obesity and Cardiac Function - The Role of Caloric Excess and its Reversal. Drug Discov Today Dis Mech 10:e41-e46
Avila, C; Huang, R J; Stevens, M V et al. (2012) Platelet mitochondrial dysfunction is evident in type 2 diabetes in association with modifications of mitochondrial anti-oxidant stress proteins. Exp Clin Endocrinol Diabetes 120:248-51
Kim, Kye-Young; Sack, Michael N (2012) Parkin in the regulation of fat uptake and mitochondrial biology: emerging links in the pathophysiology of Parkinson's disease. Curr Opin Lipidol 23:201-5

Showing the most recent 10 out of 26 publications