The Protein Level of PGC-1α, a Key Metabolic Regulator, Is Controlled by NADH-NQO1

被引：83

作者：

Adamovich, Yaarit ^{[1
]}

Shlomai, Amir ^{[1
]}

Tsvetkov, Peter ^{[1
]}

Umansky, Kfir B. ^{[1
]}

Reuven, Nina ^{[1
]}

Estall, Jennifer L. ^{[2
,3
]}

Spiegelman, Bruce M. ^{[2
,3
]}

Shaul, Yosef ^{[1
]}

机构：

[1] Weizmann Inst Sci, Dept Mol Genet, IL-76100 Rehovot, Israel

[2] Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA

[3] Dana Farber Canc Inst, Div Metab & Chron Dis, Boston, MA 02115 USA

来源：

MOLECULAR AND CELLULAR BIOLOGY | 2013年 / 33卷 / 13期

基金：

以色列科学基金会;

关键词：

TRANSCRIPTIONAL COACTIVATOR PGC-1; 20S PROTEASOMAL DEGRADATION; NAD(P)H-QUINONE OXIDOREDUCTASE-1 NQO1; INTRINSICALLY UNSTRUCTURED PROTEINS; NAD(P)H QUINONE OXIDOREDUCTASE-1; INDUCED SKIN-CANCER; SKELETAL-MUSCLE; HEPATIC GLUCONEOGENESIS; ENERGY-METABOLISM; REDOX STATE;

D O I：

10.1128/MCB.01672-12

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

070307 [化学生物学]; 071010 [生物化学与分子生物学];

摘要：

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

引用

页码：2603 / 2613

页数：11

共 77 条

[1]

c-Fos Proteasomal Degradation Is Activated by a Default Mechanism, and Its Regulation by NAD(P)H:Quinone Oxidoreductase 1 Determines c-Fos Serum Response Kinetics [J].