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. 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
Fiscal Year
Total Cost
Indirect Cost
National Heart, Lung, and Blood Institute
Zip Code
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
Kendrick, Agnieszka A; Choudhury, Mahua; Rahman, Shaikh M et al. (2011) Fatty liver is associated with reduced SIRT3 activity and mitochondrial protein hyperacetylation. Biochem J 433:505-14
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

Showing the most recent 10 out of 21 publications