Induced polymerization of mammalian acetyl-CoA carboxylase by MIG12 provides a tertiary level of regulation of fatty acid synthesis.
Proc Natl Acad Sci U S A
; 107(21): 9626-31, 2010 May 25.
Article
em En
| MEDLINE
| ID: mdl-20457939
ABSTRACT
Acetyl-CoA carboxylase (ACC), the first committed enzyme in fatty acid (FA) synthesis, is regulated by phosphorylation/dephosphorylation, transcription, and an unusual mechanism of protein polymerization. Polymerization of ACC increases enzymatic activity and is induced in vitro by supraphysiological concentrations of citrate (> 5 mM). Here, we show that MIG12, a 22 kDa cytosolic protein of previously unknown function, binds to ACC and lowers the threshold for citrate activation into the physiological range (< 1 mM). In vitro, recombinant MIG12 induced polymerization of ACC (as determined by nondenaturing gels, FPLC, and electron microscopy) and increased ACC activity by > 50-fold in the presence of 1 mM citrate. In vivo, overexpression of MIG12 in liver induced ACC polymerization, increased FA synthesis, and produced triglyceride accumulation and fatty liver. Thus, in addition to its regulation by phosphorylation and transcription, ACC is regulated at a tertiary level by MIG12, which facilitates ACC polymerization and enhances enzymatic activity.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Acetil-CoA Carboxilase
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Multimerização Proteica
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Ácidos Graxos
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Proteínas Associadas aos Microtúbulos
Limite:
Animals
Idioma:
En
Ano de publicação:
2010
Tipo de documento:
Article