| Yazarlar |
Prof. Dr. Özkan ÖZDEN
Kafkas Üniversitesi, Türkiye |
Seong-Hoon Park
Türkiye |
|
Brett A Wagner
Türkiye |
|
Song Ha Yong
Türkiye |
|
Yueming Zhu
Türkiye |
|
Athanassios Vassilopoulos
Türkiye |
|
Barbara Jung
Türkiye |
|
Garry R Buettner
Türkiye |
|
David Gius
Türkiye |
| Özet |
| Pyruvate dehydrogenase E1α (PDHA1) is the first component enzyme of the pyruvate dehydrogenase (PDH) complex that transforms pyruvate, via pyruvate decarboxylation, into acetyl-CoA that is subsequently used by both the citric acid cycle and oxidative phosphorylation to generate ATP. As such, PDH links glycolysis and oxidative phosphorylation in normal as well as cancer cells. Herein we report that SIRT3 interacts with PDHA1 and directs its enzymatic activity via changes in protein acetylation. SIRT3 deacetylates PDHA1 lysine 321 (K321), and a PDHA1 mutant mimicking a deacetylated lysine (PDHA1(K321R)) increases PDH activity, compared to the K321 acetylation mimic (PDHA1(K321Q)) or wild-type PDHA1. Finally, PDHA1(K321Q) exhibited a more transformed in vitro cellular phenotype compared to PDHA1(K321R). These results suggest that the acetylation of PDHA1 provides another layer of enzymatic regulation, in addition to phosphorylation, involving a reversible acetyllysine, suggesting that the acetylome, as well as the kinome, links glycolysis to respiration. |
| Anahtar Kelimeler |
| Pyruvate dehydrogenase | SIRT3 | PDHA1 | Acetylation | Carcinogenesis | Warburg | Free radicals |
| Makale Türü | Özgün Makale |
| Makale Alt Türü | SSCI, AHCI, SCI, SCI-Exp dergilerinde yayımlanan tam makale |
| Dergi Adı | FREE RADICAL BIOLOGY AND MEDICINE |
| Dergi ISSN | 0891-5849 |
| Dergi Tarandığı Indeksler | SCI |
| Makale Dili | İngilizce |
| Basım Tarihi | 11-2014 |
| Cilt No | 76 |
| Sayfalar | 163 / 172 |
| Doi Numarası | 10.1016/j.freeradbiomed.2014.08.001 |
| Makale Linki | http://dx.doi.org/10.1016/j.freeradbiomed.2014.08.001 |
| Atıf Sayıları | |
| WoS | 155 |
