Browse

Increased O-GlcNAcylation of Drp1 by amyloid-beta promotes mitochondrial fission and dysfunction in neuronal cells

Cited 0 time in Web of Science Cited 0 time in Scopus
Authors
Park, So Jung; Bae, Ji-Eun; Jo, Doo Sin; Kim, Joon Bum; Park, Na Yeon; Fang, Jianguo; Jung, Yong-Keun; Jo, Dong Gyu; Cho, Dong-Hyung
Issue Date
2021-01-09
Publisher
BMC
Citation
Molecular Brain. 2021 Jan 09;14(1):6
Keywords
Drp1O-GlcNAcylationMitochondrial fssionAmyloid-betaAlzheimer’s disease
Abstract
As a dynamic organelle, mitochondria continuously fuse and divide with adjacent mitochondria. Imbalance in mitochondria dynamics leads to their dysfunction, which implicated in neurodegenerative diseases. However, how mitochondria alteration and glucose defect contribute to pathogenesis of Alzheimers disease (AD) is still largely unknown. Dynamin‐related protein 1 (Drp1) is an essential regulator for mitochondria fission. Among various posttranslational modifications, O-GlcNAcylation plays a role as a sensor for nutrient and oxidative stress. In this study, we identified that Drp1 is regulated by O-GlcNAcylation in AD models. Treatment of Aβ as well as PugNAc resulted in mitochondrial fragmentation in neuronal cells. Moreover, we found that AD mice brain exhibits an upregulated Drp1 O-GlcNAcylation. However, depletion of OGT inhibited Drp1 O-GlcNAcylation in Aβ-treated cells. In addition, overexpression of O-GlcNAc defective Drp1 mutant (T585A and T586A) decreased Drp1 O-GlcNAcylation and Aβ-induced mitochondria fragmentation. Taken together, these finding suggest that Aβ regulates mitochondrial fission by increasing O-GlcNAcylation of Drp1.
ISSN
1756-6606
Language
English
URI
https://hdl.handle.net/10371/173455
DOI
https://doi.org/10.1186/s13041-020-00727-w
Files in This Item:
Appears in Collections:
College of Natural Sciences (자연과학대학)Dept. of Biological Sciences (생명과학부)Journal Papers (저널논문_생명과학부)
  • mendeley

Items in S-Space are protected by copyright, with all rights reserved, unless otherwise indicated.

Browse