The role of perturbations in mitochondrial function and in cellular nutrient handling is important in the development and progression of diabetes. Candidate proteins identified that may modulate the nutrient handling and mitochondrial regulatory progrmas in diabetes and nutrient overload have been identified and these are being characterized via functional genomics to evaluate their role in the development of metabolic perturbations and mitochondrial dysfunction in diabetes and obesity. 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.

Project Start
Project End
Budget Start
Budget End
Support Year
7
Fiscal Year
2013
Total Cost
$759,076
Indirect Cost
Name
National Heart, Lung, and Blood Institute
Department
Type
DUNS #
City
State
Country
Zip Code
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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
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Kim, Kye-Young; Stevens, Mark V; Akter, M Hasina et al. (2011) Parkin is a lipid-responsive regulator of fat uptake in mice and mutant human cells. J Clin Invest 121:3701-12
Liu, Hongjun; Fergusson, Maria M; Wu, J Julie et al. (2011) Wnt signaling regulates hepatic metabolism. Sci Signal 4:ra6
Bao, Jianjun; Sack, Michael N (2010) Protein deacetylation by sirtuins: delineating a post-translational regulatory program responsive to nutrient and redox stressors. Cell Mol Life Sci 67:3073-87
Pagel-Langenickel, Ines; Bao, Jianjun; Pang, Liyan et al. (2010) The role of mitochondria in the pathophysiology of skeletal muscle insulin resistance. Endocr Rev 31:25-51
Bao, Jianjun; Scott, Iain; Lu, Zhongping et al. (2010) SIRT3 is regulated by nutrient excess and modulates hepatic susceptibility to lipotoxicity. Free Radic Biol Med 49:1230-7
Sack, Michael N (2009) Type 2 diabetes, mitochondrial biology and the heart. J Mol Cell Cardiol 46:842-9

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