Mitochondrial CoQ deficiency is a common driver of mitochondrial oxidants and insulin resistance.
eLife Sciences Publications, Ltd ; //dx.doi.org/10.7554/elife.32111 ; Elife, 2018
academicJournal
Zugriff:
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.
Titel: |
Mitochondrial CoQ deficiency is a common driver of mitochondrial oxidants and insulin resistance.
|
---|---|
Autor/in / Beteiligte Person: | Fazakerley, Daniel J ; Chaudhuri, Rima ; Yang, Pengyi ; 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 Yh ; Chen, Daniel L ; Samocha-Bonet, Dorit ; Greenfield, Jerry R ; Hoehn, Kyle L ; Stocker, Roland ; James, David E |
Link: | |
Veröffentlichung: | eLife Sciences Publications, Ltd ; //dx.doi.org/10.7554/elife.32111 ; Elife, 2018 |
Medientyp: | academicJournal |
DOI: | 10.17863/CAM.56858 |
Schlagwort: |
|
Sonstiges: |
|