Mitochondrial CoQ deficiency is a common driver of mitochondrial oxidants and insulin resistance
Journal article
Fazakerley, Daniel J., Chaudhuri, Rima, Yang, Pengyi, Maghzal, Ghassan J., Thomas, Kristen C., Krycer, James R., Humphrey, Sean J., Parker, Benjamin, Fisher-Wellman, Kelsey H., Meoli, Christopher C., Hoffman, Nolan, Diskin, Ciana, Burchfield, James G., Cowley, Mark J., Kaplan, Warren, Modrusan, Zora, Kolumam, Ganesh, Yang, Jean Y. H., Chen, Daniel L., ... James, David E.. (2018). Mitochondrial CoQ deficiency is a common driver of mitochondrial oxidants and insulin resistance. eLife. 7, pp. 1 - 38. https://doi.org/10.7554/eLife.32111
Authors | Fazakerley, Daniel J., Chaudhuri, Rima, Yang, Pengyi, Maghzal, Ghassan J., Thomas, Kristen C., Krycer, James R., Humphrey, Sean J., Parker, Benjamin, Fisher-Wellman, Kelsey H., Meoli, Christopher C., Hoffman, Nolan, Diskin, Ciana, Burchfield, James G., Cowley, Mark J., Kaplan, Warren, Modrusan, Zora, Kolumam, Ganesh, Yang, Jean Y. H., Chen, Daniel L., Samocha-Bonet, Dorit, Greenfield, Jerry R., Hoehn, Kyle L., Stocker, Roland and James, David E. |
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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. |
Year | 2018 |
Journal | eLife |
Journal citation | 7, pp. 1 - 38 |
Publisher | eLife Sciences Publications Ltd |
ISSN | 2050-084X |
Digital Object Identifier (DOI) | https://doi.org/10.7554/eLife.32111 |
Scopus EID | 2-s2.0-85043492603 |
Open access | Open access |
Page range | 1 - 38 |
Research Group | Mary MacKillop Institute for Health Research |
Publisher's version | |
Place of publication | United Kingdom |
Editors | R. Schekman |
https://acuresearchbank.acu.edu.au/item/8q630/mitochondrial-coq-deficiency-is-a-common-driver-of-mitochondrial-oxidants-and-insulin-resistance
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