Title : Modulation of dynamin-related protein 1 ( DRP1 ) function by increased O-linked-β-N-acetylglucosamine modification (O-GlcNAc) in cardiac myocytes
Abstract :
O-linked-N-acetyl-glucosamine glycosylation (O-GlcNAcylation) of the serine and threonine residues of cellular proteins is a dynamic process and affects phosphorylation
Prolonged O-GlcNAcylation has been linked to diabetes-related complications, including mitochondrial dysfunction
Mitochondria are dynamically remodeling organelles, that constantly fuse (fusion) and divide (fission)
An imbalance of this process affects mitochondrial function
In this study, we found that dynamin-related protein 1 ( DRP1 ) is O-GlcNAcylated in cardiomyocytes at threonine 585 and 586
O-GlcNAcylation was significantly enhanced by the chemical inhibition of N-acetyl-glucosaminidase
Increased O-GlcNAcylation decreases the phosphorylation of DRP1 at serine 637 , which is known to regulate DRP1 function
In fact, increased O-GlcNAcylation augments the level of the GTP-bound active form of DRP1 and induces translocation of DRP1 from the cytoplasm to mitochondria
Mitochondrial fragmentation and decreased mitochondrial membrane potential also accompany the increased O-GlcNAcylation
In conclusion, this report shows, for the first time, that O-GlcNAcylation modulates DRP1 functionality in cardiac muscle cells