Mitochondrial CoQ deficiency is a common driver of mitochondrial oxidants and insulin resistance.
Elife
; 72018 02 06.
Article
en En
| MEDLINE
| ID: mdl-29402381
ABSTRACT
Insulin resistance in muscle, adipocytes and liver is a gateway to a number of metabolic diseases. Here, we show a selective deficiency in mitochondrial coenzyme Q (CoQ) in insulin-resistant adipose and muscle tissue. This defect was observed in a range of in vitro insulin resistance models and adipose tissue from insulin-resistant humans and was concomitant with lower expression of mevalonate/CoQ biosynthesis pathway proteins in most models. Pharmacologic or genetic manipulations that decreased mitochondrial CoQ triggered mitochondrial oxidants and insulin resistance while CoQ supplementation in either insulin-resistant cell models or mice restored normal insulin sensitivity. Specifically, lowering of mitochondrial CoQ caused insulin resistance in adipocytes as a result of increased superoxide/hydrogen peroxide production via complex II. These data suggest that mitochondrial CoQ is a proximal driver of mitochondrial oxidants and insulin resistance, and that mechanisms that restore mitochondrial CoQ may be effective therapeutic targets for treating insulin resistance.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Ataxia
/
Resistencia a la Insulina
/
Tejido Adiposo
/
Ubiquinona
/
Oxidantes
/
Debilidad Muscular
/
Enfermedades Mitocondriales
/
Mitocondrias
/
Músculos
Tipo de estudio:
Diagnostic_studies
Límite:
Animals
/
Humans
Idioma:
En
Revista:
Elife
Año:
2018
Tipo del documento:
Article
País de afiliación:
Australia