Blocked O-GlcNAc cycling alters mitochondrial morphology, function, and mass
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...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Nature Publishing Group UK
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8586252/ https://www.ncbi.nlm.nih.gov/pubmed/34764359 http://dx.doi.org/10.1038/s41598-021-01512-y |
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author | Akinbiyi, Elizabeth O. Abramowitz, Lara K. Bauer, Brianna L. Stoll, Maria S. K. Hoppel, Charles L. Hsiao, Chao-Pin Hanover, John A. Mears, Jason A. |
author_facet | Akinbiyi, Elizabeth O. Abramowitz, Lara K. Bauer, Brianna L. Stoll, Maria S. K. Hoppel, Charles L. Hsiao, Chao-Pin Hanover, John A. Mears, Jason A. |
author_sort | Akinbiyi, Elizabeth O. |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-8586252 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-85862522021-11-12 Blocked O-GlcNAc cycling alters mitochondrial morphology, function, and mass Akinbiyi, Elizabeth O. Abramowitz, Lara K. Bauer, Brianna L. Stoll, Maria S. K. Hoppel, Charles L. Hsiao, Chao-Pin Hanover, John A. Mears, Jason A. Sci Rep Article 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. Nature Publishing Group UK 2021-11-11 /pmc/articles/PMC8586252/ /pubmed/34764359 http://dx.doi.org/10.1038/s41598-021-01512-y Text en © The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Article Akinbiyi, Elizabeth O. Abramowitz, Lara K. Bauer, Brianna L. Stoll, Maria S. K. Hoppel, Charles L. Hsiao, Chao-Pin Hanover, John A. Mears, Jason A. Blocked O-GlcNAc cycling alters mitochondrial morphology, function, and mass |
title | Blocked O-GlcNAc cycling alters mitochondrial morphology, function, and mass |
title_full | Blocked O-GlcNAc cycling alters mitochondrial morphology, function, and mass |
title_fullStr | Blocked O-GlcNAc cycling alters mitochondrial morphology, function, and mass |
title_full_unstemmed | Blocked O-GlcNAc cycling alters mitochondrial morphology, function, and mass |
title_short | Blocked O-GlcNAc cycling alters mitochondrial morphology, function, and mass |
title_sort | blocked o-glcnac cycling alters mitochondrial morphology, function, and mass |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8586252/ https://www.ncbi.nlm.nih.gov/pubmed/34764359 http://dx.doi.org/10.1038/s41598-021-01512-y |
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