| First Author | Cha MY | Year | 2015 |
| Journal | Hum Mol Genet | Volume | 24 |
| Issue | 22 | Pages | 6492-504 |
| PubMed ID | 26358770 | Mgi Jnum | J:226496 |
| Mgi Id | MGI:5697596 | Doi | 10.1093/hmg/ddv358 |
| Citation | Cha MY, et al. (2015) Mitochondrial ATP synthase activity is impaired by suppressed O-GlcNAcylation in Alzheimer's disease. Hum Mol Genet 24(22):6492-504 |
| abstractText | Glycosylation with O-linked beta-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 alpha (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 Abeta-treated cells. Indeed, Abeta 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 Abeta-induced impairment in ATP production and ATPase activity. These results indicate that Abeta-mediated reduction of ATP synthase activity in AD pathology results from direct binding between Abeta and ATP synthase and inhibition of O-GlcNAcylation of Thr432 residue on ATP5A. |
