Mitochondrial CoQ deficiency is a common driver of mitochondrial oxidants and insulin resistance

Elife. 2018 Feb 6;7:e32111. doi: 10.7554/eLife.32111.

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.

Keywords: Coenzyme Q; Insulin; Insulin resistance; Mitochondria; Oxidants; Ubiquinone; cell biology; human; human biology; medicine; mouse.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adipocytes / physiology
  • Adipose Tissue / pathology*
  • Animals
  • Ataxia*
  • Humans
  • Insulin Resistance*
  • Mice
  • Mitochondria / pathology*
  • Mitochondrial Diseases / physiopathology*
  • Muscle Weakness*
  • Muscles / pathology*
  • Oxidants / metabolism*
  • Sensitivity and Specificity
  • Ubiquinone / deficiency*

Substances

  • Oxidants
  • Ubiquinone

Supplementary concepts

  • Coenzyme Q10 Deficiency