Cited by 95Alzheimer's disease research and treatmentsGlycosylation and Glycoproteins ResearchMitochondrial Function and Pathology

Mitochondrial ATP synthase activity is impaired by suppressed O-GlcNAcylation in Alzheimer's disease

Open access
Cha, Moon-Yong, Cho, Hyun Jin, Kim, Chaeyoung, Jung, Yang Ouk, Kang, Min Jueng, Murray, Melissa E., Hong, Hyun Seok, Choi, Young-Joo +11 more·2015·Human Molecular Genetics

Abstract

Glycosylation with O-linked β-N-acetylglucosamine (O-GlcNAc) is one of the protein glycosylations affecting various intracellular events. However, the role of O-GlcNAcylation in neurodegenerative diseases such as Alzheimer's disease (AD) is poorly understood. Mitochondrial adenosine 5'-triphosphate (ATP) synthase is a multiprotein complex that synthesizes ATP from ADP and Pi. Here, we found that ATP synthase subunit α (ATP5A) was O-GlcNAcylated at Thr432 and ATP5A O-GlcNAcylation was decreased in the brains of AD patients and transgenic mouse model, as well as Aβ-treated cells. Indeed, Aβ bound to ATP synthase directly and reduced the O-GlcNAcylation of ATP5A by inhibition of direct interaction between ATP5A and mitochondrial O-GlcNAc transferase, resulting in decreased ATP production and ATPase activity. Furthermore, treatment of O-GlcNAcase inhibitor rescued the Aβ-induced impairment in ATP production and ATPase activity. These results indicate that Aβ-mediated reduction of ATP synthase activity in AD pathology results from direct binding between Aβ and ATP synthase and inhibition of O-GlcNAcylation of Thr432 residue on ATP5A.

Integrity signals

Registry

Crossref · 10.1093/hmg/ddv358

Cites

47 of 47 references verified0 citation errors · 0 not checkable

Statistics

Recomputing p-values needs the paper’s full text.

Claims the paper makes

We couldn’t retrieve this paper’s full text, so its claims and self-check weren’t run. The registry and citation checks still apply.

Cites

Flagged first, then by citations

Cited by

Sorted by citations

Authors
Cha, M.-Y., Cho, H. J., Kim, C., Jung, Y. O., Kang, M. J., Murray, M. E., Hong, H. S., Choi, Y.-J., Choi, H., Kim, D. K., Choi, H., Kim, J., Dickson, D. W., Song, H. K., Cho, J. W., Yi, E. C., Kim, J., Jin, S. M., & Mook-Jung, I.
Affiliations
  • Seoul National University (KR)
  • Mayo Clinic (US)
  • Korea University (KR)
  • Medifron (South Korea) (KR)
  • Yonsei University (KR)
Corresponding author
Jin, Seok Min
Venue
Human Molecular Genetics
Published
2015-09-10
Volume
24
Issue
22
Pages
6492-6504
ISSN
  • 0964-6906 (ISSN-L)
  • 1460-2083
OpenAlex
W1886846543
Cited by
95
References
47
Citations by year
2026: 9 · 2025: 5 · 2024: 4 · 2023: 5 · 2022: 15 · 2021: 18 · 2020: 10 · 2019: 5 · 2018: 13 · 2017: 8 · 2016: 2 · 2015: 1
FWCI
5.15
Type
journal article
Language
en
Open access
Locations
  • Human Molecular Genetics (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (submittedVersion)
Funders
  • National Research Foundation (2015R1A2A1A05001794, 2014M3C7A1046047, 2015M3C7A1028790)
  • Medical Research Center (2011-0030738)
  • KIST Institutional Program (2E24242-13-135, NRF-2013R1A2A1A01008067, GHR Foundation (JK), NIH, AG016574)
  • Jacoby Professorship of Alzheimer Research
  • Donors Cure Foundation
  • Einstein Aging Study (NIH P01-AG03949)
Topics
  • Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Glycosylation and Glycoproteins Research
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
Keywords
O-GlcNAcylation, Alzheimer's disease, mitochondrial ATP synthase, ATP5A, amyloid-beta, O-GlcNAc transferase, protein glycosylation, ATP production, ATPase activity, neurodegeneration, transgenic mouse model
MeSH terms
Acetylglucosamine, Adenosine Triphosphate, Alzheimer Disease, Animals, beta-N-Acetylhexosaminidases, Cricetulus, Disease Models, Animal, Glycosylation, HeLa Cells, Humans, Mice, Transgenic, Mitochondria, Oxidative Phosphorylation Coupling Factors, Protein Processing, Post-Translational, CHO Cells, N-Acetylglucosaminyltransferases, Mitochondrial Proton-Translocating ATPases, Mice

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review