The protein level of PGC-1?, a key metabolic regulator, is controlled by NADH-NQO1.

ABSTRACT: PGC-1? is a key transcription coactivator regulating energy metabolism in a tissue-specific manner. PGC-1? 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-1? as an IDP and demonstrate that it is susceptible to 20S proteasomal degradation by default. We further demonstrate that PGC-1? degradation is inhibited by NQO1, a 20S gatekeeper protein. NQO1 binds and protects PGC-1? from degradation in an NADH-dependent manner. Using different cellular physiological settings, we also demonstrate that NQO1-mediated PGC-1? protection plays an important role in controlling both basal and physiologically induced PGC-1? protein level and activity. Our findings link NQO1, a cellular redox sensor, to the metabolite-sensing network that tunes PGC-1? expression and activity in regulating energy metabolism.

SUBMITTER: Adamovich Y 

PROVIDER: S-EPMC3700121 | biostudies-literature | 2013 Jul

REPOSITORIES: biostudies-literature