Atpenins, potent and specific inhibitors of mitochondrial complex II (succinate-ubiquinone oxidoreductase).
Enzymes in the mitochondrial respiratory chain are involved in various physiological events in addition to their essential role in the production of ATP by oxidative phosphorylation. The use of specific and potent inhibitors of complex I (NADH-ubiquinone reductase) and complex III (ubiquinol-cytochrome c reductase), such as rotenone and antimycin, respectively, has allowed determination of the role of these enzymes in physiological processes. However, unlike complexes I, III, and IV (cytochrome c oxidase), there are few potent and specific inhibitors of complex II (succinate-ubiquinone reductase) that have been described. In this article, we report that atpenins potently and specifically inhibit the succinate-ubiquinone reductase activity of mitochondrial complex II. Therefore, atpenins may be useful tools for clarifying the biochemical and structural properties of complex II, as well as for determining its physiological roles in mammalian tissues.
Miyadera
Hiroko
H
Department of Biomedical Chemistry, Graduate School of Medicine, University of Tokyo, Bunkyo-ku, Tokyo 113-0033, Japan.
Shiomi
Kazuro
K
Ui
Hideaki
H
Yamaguchi
Yuichi
Y
Masuma
Rokuro
R
Tomoda
Hiroshi
H
Miyoshi
Hideto
H
Osanai
Arihiro
A
Kita
Kiyoshi
K
Omura
Satoshi
S
D000818:Animals; D000935:Antifungal Agents / Q000494:pharmacology*; D001665:Binding Sites; D002417:Cattle; D042963:Electron Transport Complex II; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D008928:Mitochondria / Q000201:enzymology*; D009097:Multienzyme Complexes / Q000037:antagonists & inhibitors* / Q000378:metabolism; D010088:Oxidoreductases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D011728:Pyridones; D051381:Rats; D013385:Succinate Dehydrogenase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D025801:Ubiquitin / Q000378:metabolism
D000935:Antifungal Agents; D004791:Enzyme Inhibitors; D009097:Multienzyme Complexes; D011728:Pyridones; D025801:Ubiquitin; C058278:atpenin A5; C058277:atpenin A4; D010088:Oxidoreductases; D042963:Electron Transport Complex II; C424907:quinol fumarate reductase; D013385:Succinate Dehydrogenase