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Mitochondrial CoQ deficiency is a common driver of mitochondrial oxidants and insulin resistance
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.
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.
Author
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
James, David E.
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
James, David E.
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.
Keywords
Date
2018
Type
Journal article
Journal
eLife
Book
Volume
7
Issue
Page Range
1-38
Article Number
ACU Department
Centre for Exercise and Nutrition
Faculty of Health Sciences
Faculty of Health Sciences
Collections
Relation URI
Source URL
Event URL
Open Access Status
Open access
License
File Access
Open