All ETDs from UAB

Advisory Committee Chair

John C Chatham

Advisory Committee Members

Scott W Ballinger

Victor M Darley-Usmar

Lori L McMahon

Martin E Young

Document Type


Date of Award


Degree Name by School

Master of Science (MS) Heersink School of Medicine


O-linked beta-N-acetylglucosamine (O-GlcNAc) is a dynamic and ubiquitous posttranslational modification of serine and threonine residues on nuclear and cytoplasmic proteins. O-GlcNAc has emerged as an important regulator of cellular processes such as cell signaling, transcription, translation, apoptosis, and cell cycle regulation, among others. O-GlcNAc is thought to be a contributor to pathologies such as hyperglycemia and insulin resistance. O-GlcNAc has been viewed as an indicator of cellular energy levels and is associated with diabetic complications under nutrient excess. Other studies have shown that a variety of stress stimuli increase the levels of protein O-GlcNAc in mammalian cells, and this increase is associated with cytoprotection. Inhibiting O-GlcNAcylation decreased cell survival in response to stress, while increased O-GlcNAcylation augmented cell survival. Many of these studies demonstrated that this cytoprotection was associated with mitochondrial proteins. Compared to the nucleo-cytoplasm, much less work has been done in elucidating the potential role of O-GlcNAc in the mitochondria. In cardiac myocytes chronically exposed to high levels of glucose, complexes of the mitochondrial respiratory chain were shown to be O-GlcNAc modified. However these modifications were associated with impaired mitochondrial respiratory function. Hyperglycemia also induces mitochondrial superoxide production, which was shown to increase hexosamine biosynthesis and O- GlcNAcylation. Reactive oxygen species production can also lead to mitochondrial respiratory dysfunction and loss of mitochondrial membrane potential. It is possible that O-GlcNAcylation of respiratory chain complexes is involved in cardioprotection. While these results may seem contradictory, O-GlcNAcylation may simply be a constitutive element in non-pathological cellular functions, including oxidative phosphorylation, and perturbations in homeostatic O-GlcNAc signaling may lead to cell and mitochondrial dysfunction. Despite the current progress, the effect of O-GlcNAc on the many functions that mitochondria perform is still relatively unknown. It is increasingly apparent that mitochondrial proteins are O-GlcNAc modified and that this modification appears to modulate the function of these proteins.



To view the content in your browser, please download Adobe Reader or, alternately,
you may Download the file to your hard drive.

NOTE: The latest versions of Adobe Reader do not support viewing PDF files within Firefox on Mac OS and if you are using a modern (Intel) Mac, there is no official plugin for viewing PDF files within the browser window.