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

Fazakerley, DJ ; Chaudhuri, R ; et al.
In: ELife, Jg. 7 (2018-02-06)
Online academicJournal
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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.

Competing Interests: DF, RC, PY, GM, KT, JK, SH, BP, KF, CM, NH, CD, JB, MC, WK, ZM, DC, DS, JG, KH, RS, DJ No competing interests declared, GK Employed by Genentech Inc. at the time the study was conducted. JY Jean YH Yang: Employed by Genentech Inc. at the time the study was conducted.

(© 2018, Fazakerley et al.)

Titel:
Mitochondrial CoQ deficiency is a common driver of mitochondrial oxidants and insulin resistance.
Autor/in / Beteiligte Person: Fazakerley, DJ ; Chaudhuri, R ; Yang, P ; Maghzal, GJ ; Thomas, KC ; Krycer, JR ; Humphrey, SJ ; Parker, BL ; Fisher-Wellman, KH ; Meoli, CC ; Hoffman, NJ ; Diskin, C ; Burchfield, JG ; Cowley, MJ ; Kaplan, W ; Modrusan, Z ; Kolumam, G ; Yang, JY ; Chen, DL ; Samocha-Bonet, D ; Greenfield, JR ; Hoehn, KL ; Stocker, R ; James, DE
Link:
Zeitschrift: ELife, Jg. 7 (2018-02-06)
Veröffentlichung: Cambridge, UK : eLife Sciences Publications, Ltd., 2012-, 2018
Medientyp: academicJournal
ISSN: 2050-084X (electronic)
DOI: 10.7554/eLife.32111
Schlagwort:
  • Adipocytes physiology
  • Animals
  • Humans
  • Mice
  • Sensitivity and Specificity
  • Adipose Tissue pathology
  • Ataxia
  • Insulin Resistance
  • Mitochondria pathology
  • Mitochondrial Diseases physiopathology
  • Muscle Weakness
  • Muscles pathology
  • Oxidants metabolism
  • Ubiquinone deficiency
Sonstiges:
  • Nachgewiesen in: MEDLINE
  • Sprachen: English
  • Publication Type: Journal Article; Research Support, Non-U.S. Gov't
  • Language: English
  • [Elife] 2018 Feb 06; Vol. 7. <i>Date of Electronic Publication: </i>2018 Feb 06.
  • MeSH Terms: Ataxia* ; Insulin Resistance* ; Muscle Weakness* ; Adipose Tissue / *pathology ; Mitochondria / *pathology ; Mitochondrial Diseases / *physiopathology ; Muscles / *pathology ; Oxidants / *metabolism ; Ubiquinone / *deficiency ; Adipocytes / physiology ; Animals ; Humans ; Mice ; Sensitivity and Specificity
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  • Grant Information: United Kingdom Wellcome Trust; 092255/Z/10/Z United Kingdom Wellcome Trust
  • Contributed Indexing: Keywords: Coenzyme Q; Insulin; Insulin resistance; Mitochondria; Oxidants; Ubiquinone; cell biology; human; human biology; medicine; mouse
  • Substance Nomenclature: 0 (Oxidants) ; 1339-63-5 (Ubiquinone)
  • SCR Disease Name: Coenzyme Q10 Deficiency
  • Entry Date(s): Date Created: 20180207 Date Completed: 20190806 Latest Revision: 20191008
  • Update Code: 20240513
  • PubMed Central ID: PMC5800848

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