Fazakerley, Daniel J and Chaudhuri, Rima and Yang, Pengyi and Maghzal, Ghassan J and Thomas, Kristen C and Krycer, James R and Humphrey, Sean J and Parker, Benjamin L and Fisher-Wellman, Kelsey H and Meoli, Christopher C and Hoffman, Nolan J and Diskin, Ciana and Burchfield, James G and Cowley, Mark J and Kaplan, Warren and Modrusan, Zora and Kolumam, Ganesh and Yang, Jean YH and Chen, Daniel L and Samocha-Bonet, Dorit and Greenfield, Jerry R and Hoehn, Kyle L and Stocker, Roland and James, David E (2018) Mitochondrial CoQ deficiency is a common driver of mitochondrial oxidants and insulin resistance. eLife, 7. pp. e32111. ISSN 2050-084X (OA)
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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.
| Item Type: | Article |
|---|---|
| Subjects: | R Medicine > R Medicine (General) |
| Depositing User: | Repository Administrator |
| Date Deposited: | 12 Feb 2018 06:12 |
| Last Modified: | 12 Feb 2018 06:12 |
| URI: | https://eprints.victorchang.edu.au/id/eprint/695 |
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