| First Author | Adamovich Y | Year | 2013 |
| Journal | Mol Cell Biol | Volume | 33 |
| Issue | 13 | Pages | 2603-13 |
| PubMed ID | 23648480 | Mgi Jnum | J:204485 |
| Mgi Id | MGI:5532637 | Doi | 10.1128/MCB.01672-12 |
| Citation | Adamovich Y, et al. (2013) The protein level of PGC-1alpha, a key metabolic regulator, is controlled by NADH-NQO1. Mol Cell Biol 33(13):2603-13 |
| abstractText | PGC-1alpha is a key transcription coactivator regulating energy metabolism in a tissue-specific manner. PGC-1alpha expression is tightly regulated, it is a highly labile protein, and it interacts with various proteins--the known attributes of intrinsically disordered proteins (IDPs). In this study, we characterize PGC-1alpha as an IDP and demonstrate that it is susceptible to 20S proteasomal degradation by default. We further demonstrate that PGC-1alpha degradation is inhibited by NQO1, a 20S gatekeeper protein. NQO1 binds and protects PGC-1alpha from degradation in an NADH-dependent manner. Using different cellular physiological settings, we also demonstrate that NQO1-mediated PGC-1alpha protection plays an important role in controlling both basal and physiologically induced PGC-1alpha protein level and activity. Our findings link NQO1, a cellular redox sensor, to the metabolite-sensing network that tunes PGC-1alpha expression and activity in regulating energy metabolism. |
