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

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 Biol

authors

Adamovich Y,Shlomai A,Tsvetkov P,Umansky KB,Reuven N,Estall JL,Spiegelman BM,Shaul Y

doi

10.1128/MCB.01672-12

subject

Has Abstract

pub_date

2013-07-01 00:00:00

pages

2603-13

issue

13

eissn

0270-7306

issn

1098-5549

pii

MCB.01672-12

journal_volume

33

pub_type

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