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- Title
Mitochondrial CoQ deficiency is a common driver of mitochondrial oxidants and insulin resistance.
- Authors
Fazakerley, Daniel J.; Chaudhuri, Rima; Pengyi Yang; Maghzal, Ghassan J.; Thomas, Kristen C.; Krycer, James R.; Humphrey, Sean J.; Parker, Benjamin L.; Fisher-Wellman, Kelsey H.; Meoli, Christopher C.; Hoffman, Nolan J.; Diskin, Ciana; Burchfield, James G.; Cowley, Mark J.; Kaplan, Warren; Modrusan, Zora; Kolumam, Ganesh; Yang, Jean Y. H.; Chen, Daniel L.; Samocha-Bonet, Dorit
- 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.
- Subjects
UBIQUINONES; MITOCHONDRIA; OXIDIZING agents; INSULIN resistance; FAT cells; METABOLIC disorders; ADIPOSE tissues; PROTEIN expression
- Publication
eLife, 2018, p1
- ISSN
2050-084X
- Publication type
Article
- DOI
10.7554/eLife.32111