High Glucose Induces Mitochondrial Dysfunction Independent of Protein O-GlcNAcylation

In this study, we tested whether high glucose-induced increases in O-GlcNAc modifications directly regulate mitochondrial function in isolated cardiomyocytes. Augmentation of O-GlcNAcylation with high glucose (33 mM) was associated with diminished basal and maximal cardiomyocyte respiration, a decreased mitochondrial reserve capacity, and lower Complex II-dependent respiration (p<0.05); however, pharmacological or genetic modulation of O-GlcNAc modifications under normal or high glucose conditions showed few significant effects on mitochondrial respiration, suggesting that O-GlcNAc does not play a major role in regulating cardiomyocyte mitochondrial function. Furthermore, an osmotic control recapitulated high glucose-induced changes to mitochondrial metabolism (p<0.05) without increasing O-GlcNAcylation. Thus, increased O-GlcNAcylation is neither sufficient nor necessary for high glucose-induced suppression of mitochondrial metabolism in isolated cardiomyocytes.

Source: BJ Energy - January 27, 2015 Category: Biochemistry Authors: S Dassanayaka, R D Readnower, J K Salabei, B W Long, A L Aird, Y Zheng, S Muthusamy, H T Facundo, B G Hill, S P Jones Tags: BJ Metabolism Source Type: research