Fazakerley 2018 Elife

[[Has title::Fazakerley 1DJ, 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 (2018) Mitochondrial CoQ deficiency is a common driver of mitochondrial oxidants and insulin resistance. Elife 7:32111.]]

» [[Has info::PMID:29402381 Open Access]]

Was written by::Fazakerley 1DJ, Was written by::Chaudhuri R, Was written by::Yang P, Was written by::Maghzal GJ, Was written by::Thomas KC, Was written by::Krycer JR, Was written by::Humphrey SJ, Was written by::Parker BL, Was written by::Fisher-Wellman KH, Was written by::Meoli CC, Was written by::Hoffman NJ, Was written by::Diskin C, Was written by::Burchfield JG, Was written by::Cowley MJ, Was written by::Kaplan W, Was written by::Modrusan Z, Was written by::Kolumam G, Was written by::Yang JY, Was written by::Chen DL, Was written by::Samocha-Bonet D, Was written by::Greenfield JR, Was written by::Hoehn KL, Was written by::Stocker R, Was written by::James DE (Was published in year::2018) Was published in journal::Elife

Abstract: [[has 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.]]

Cited by

• Komlódi T, Cardoso LHD, Doerrier C, Moore AL, Rich PR, Gnaiger E (2021) Coupling and pathway control of coenzyme Q redox state and respiration in isolated mitochondria. Bioenerg Commun 2021.3. https://doi.org/10.26124/bec:2021-0003

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