Blocked O-GlcNAc cycling alters mitochondrial morphology, function, and mass

Abstract 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 morph...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Elizabeth O. Akinbiyi, Lara K. Abramowitz, Brianna L. Bauer, Maria S. K. Stoll, Charles L. Hoppel, Chao-Pin Hsiao, John A. Hanover, Jason A. Mears
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/9048e2672c6344cea6e502b9ebc484a0
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:9048e2672c6344cea6e502b9ebc484a0
record_format	dspace
spelling	oai:doaj.org-article:9048e2672c6344cea6e502b9ebc484a02021-11-14T12:17:28ZBlocked O-GlcNAc cycling alters mitochondrial morphology, function, and mass10.1038/s41598-021-01512-y2045-2322https://doaj.org/article/9048e2672c6344cea6e502b9ebc484a02021-11-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-01512-yhttps://doaj.org/toc/2045-2322Abstract 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.Elizabeth O. AkinbiyiLara K. AbramowitzBrianna L. BauerMaria S. K. StollCharles L. HoppelChao-Pin HsiaoJohn A. HanoverJason A. MearsNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-16 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Elizabeth O. Akinbiyi Lara K. Abramowitz Brianna L. Bauer Maria S. K. Stoll Charles L. Hoppel Chao-Pin Hsiao John A. Hanover Jason A. Mears Blocked O-GlcNAc cycling alters mitochondrial morphology, function, and mass
description	Abstract 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	article
author	Elizabeth O. Akinbiyi Lara K. Abramowitz Brianna L. Bauer Maria S. K. Stoll Charles L. Hoppel Chao-Pin Hsiao John A. Hanover Jason A. Mears
author_facet	Elizabeth O. Akinbiyi Lara K. Abramowitz Brianna L. Bauer Maria S. K. Stoll Charles L. Hoppel Chao-Pin Hsiao John A. Hanover Jason A. Mears
author_sort	Elizabeth O. Akinbiyi
title	Blocked O-GlcNAc cycling alters mitochondrial morphology, function, and mass
title_short	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_sort	blocked o-glcnac cycling alters mitochondrial morphology, function, and mass
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/9048e2672c6344cea6e502b9ebc484a0
work_keys_str_mv	AT elizabethoakinbiyi blockedoglcnaccyclingaltersmitochondrialmorphologyfunctionandmass AT larakabramowitz blockedoglcnaccyclingaltersmitochondrialmorphologyfunctionandmass AT briannalbauer blockedoglcnaccyclingaltersmitochondrialmorphologyfunctionandmass AT mariaskstoll blockedoglcnaccyclingaltersmitochondrialmorphologyfunctionandmass AT charleslhoppel blockedoglcnaccyclingaltersmitochondrialmorphologyfunctionandmass AT chaopinhsiao blockedoglcnaccyclingaltersmitochondrialmorphologyfunctionandmass AT johnahanover blockedoglcnaccyclingaltersmitochondrialmorphologyfunctionandmass AT jasonamears blockedoglcnaccyclingaltersmitochondrialmorphologyfunctionandmass
_version_	1718429300869300224

Blocked O-GlcNAc cycling alters mitochondrial morphology, function, and mass

Ejemplares similares