Blocked O-GlcNAc cycling alters mitochondrial morphology, function, and mass
| Autor: | Lara K. Abramowitz, John A. Hanover, Charles L. Hoppel, Elizabeth O. Akinbiyi, Jason A. Mears, Brianna L. Bauer, Chao-Pin Hsiao, Maria S.K. Stoll |
|---|---|
| Rok vydání: | 2021 |
| Předmět: |
Dynamins
Glycosylation Acylation Science Glycobiology Oxidative phosphorylation GTPase Mitochondrion N-Acetylglucosaminyltransferases Mitochondrial Dynamics Biochemistry Mitochondria Heart Oxidative Phosphorylation Article Cell Line Mice chemistry.chemical_compound Multienzyme Complexes Cell Line Tumor Animals Humans Cellular localization Mice Knockout Organelles Multidisciplinary Mitochondrial proteins HCT116 Cells Electron transport chain Mitochondria Cell biology CNS cancer Cytosol Glucose chemistry Medicine Mitochondrial fission Protein Processing Post-Translational Signal Transduction Post-translational modifications |
| Zdroj: | Scientific Reports Scientific Reports, Vol 11, Iss 1, Pp 1-16 (2021) |
| ISSN: | 2045-2322 |
| Popis: | O-GlcNAcylation is a prevalent form of glycosylation that regulates proteins within the cytosol, nucleus, and mitochondria. The O-GlcNAc modification can affect protein cellular localization, function, and signaling interactions. The specific impact of O-GlcNAcylation on mitochondrial morphology and function has been elusive. In this manuscript, the role of O-GlcNAcylation on mitochondrial fission, oxidative phosphorylation (Oxphos), and the activity of electron transport chain (ETC) complexes were evaluated. In a cellular environment with hyper O-GlcNAcylation due to the deletion of O-GlcNAcase (OGA), mitochondria showed a dramatic reduction in size and a corresponding increase in number and total mitochondrial mass. Because of the increased mitochondrial content, OGA knockout cells exhibited comparable coupled mitochondrial Oxphos and ATP levels when compared to WT cells. However, we observed reduced protein levels for complex I and II when comparing normalized mitochondrial content and reduced linked activity for complexes I and III when examining individual ETC complex activities. In assessing mitochondrial fission, we observed increased amounts of O-GlcNAcylated dynamin-related protein 1 (Drp1) in cells genetically null for OGA and in glioblastoma cells. Individual regions of Drp1 were evaluated for O-GlcNAc modifications, and we found that this post-translational modification (PTM) was not limited to the previously characterized residues in the variable domain (VD). Additional modification sites are predicted in the GTPase domain, which may influence enzyme activity. Collectively, these results highlight the impact of O-GlcNAcylation on mitochondrial dynamics and ETC function and mimic the changes that may occur during glucose toxicity from hyperglycemia. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Full text from SpringerLink