Abstract:
:PGC-1α is a key transcription coactivator regulating energy metabolism in a tissue-specific manner. PGC-1α 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-1α as an IDP and demonstrate that it is susceptible to 20S proteasomal degradation by default. We further demonstrate that PGC-1α degradation is inhibited by NQO1, a 20S gatekeeper protein. NQO1 binds and protects PGC-1α from degradation in an NADH-dependent manner. Using different cellular physiological settings, we also demonstrate that NQO1-mediated PGC-1α protection plays an important role in controlling both basal and physiologically induced PGC-1α protein level and activity. Our findings link NQO1, a cellular redox sensor, to the metabolite-sensing network that tunes PGC-1α expression and activity in regulating energy metabolism.
journal_name
Mol Cell Bioljournal_title
Molecular and cellular biologyauthors
Adamovich Y,Shlomai A,Tsvetkov P,Umansky KB,Reuven N,Estall JL,Spiegelman BM,Shaul Ydoi
10.1128/MCB.01672-12subject
Has Abstractpub_date
2013-07-01 00:00:00pages
2603-13issue
13eissn
0270-7306issn
1098-5549pii
MCB.01672-12journal_volume
33pub_type
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