Mitochondrial CoQ deficiency is a common driver of mitochondrial oxidants and insulin resistance
In: eLife, Jg. 7 (2018-02-01)
Online
academicJournal
Zugriff:
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.
Titel: |
Mitochondrial CoQ deficiency is a common driver of mitochondrial oxidants and insulin resistance
|
---|---|
Autor/in / Beteiligte Person: | Daniel J Fazakerley ; Chaudhuri, Rima ; Yang, Pengyi ; Ghassan J Maghzal ; Kristen C Thomas ; James R Krycer ; Sean J Humphrey ; Benjamin L Parker ; Kelsey H Fisher-Wellman ; Christopher C Meoli ; Nolan J Hoffman ; Diskin, Ciana ; James G Burchfield ; Mark J Cowley ; Kaplan, Warren ; Modrusan, Zora ; Kolumam, Ganesh ; Jean YH Yang ; Daniel L Chen ; Samocha-Bonet, Dorit ; Jerry R Greenfield ; Kyle L Hoehn ; Stocker, Roland ; David E James |
Link: | |
Zeitschrift: | eLife, Jg. 7 (2018-02-01) |
Veröffentlichung: | eLife Sciences Publications Ltd, 2018 |
Medientyp: | academicJournal |
ISSN: | 2050-084X (print) |
DOI: | 10.7554/eLife.32111 |
Schlagwort: |
|
Sonstiges: |
|