Atrazine binds to F1F0-ATP synthase and inhibits mitochondrial function in sperm.
Atrazine is a widely used triazine herbicide. Although controversy still exists, a number of recent studies have described its adverse effects on various animals including humans. Of particular interest is its effects on reproductive capacity. In this study, we investigated the mechanisms underlying the adverse effects of atrazine, with a focus on its effects on sperm. Here we show evidence that mitochondrial F(1)F(0)-ATP synthase is a molecular target of atrazine. A series of experiments with sperm and isolated mitochondria suggest that atrazine inhibits mitochondrial function through F(1)F(0)-ATP synthase. Moreover, affinity purification using atrazine as a ligand demonstrates that F(1)F(0)-ATP synthase is a major atrazine-binding protein in cells. The inhibitory activity against mitochondria and F(1)F(0)-ATP synthase is not limited to atrazine but is likely to be applicable to other triazine-based compounds. Thus, our findings may have wide relevance to pharmacology and toxicology.
Hase
Yasuyoshi
Y
Graduate School of Bioscience and Biotechnology, Tokyo Institute of Technology, 4259 Nagatsuta-cho, Yokohama 226-8501, Japan.
Tatsuno
Michiko
M
Nishi
Takeyuki
T
Kataoka
Kosuke
K
Kabe
Yasuaki
Y
Yamaguchi
Yuki
Y
Ozawa
Nobuaki
N
Natori
Michiya
M
Handa
Hiroshi
H
Watanabe
Hajime
H
D000328:Adult; D001280:Atrazine / Q000008:administration & dosage*; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D006540:Herbicides / Q000008:administration & dosage; D006801:Humans; D008297:Male; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects / Q000502:physiology; D008928:Mitochondria / Q000187:drug effects / Q000502:physiology*; D006180:Proton-Translocating ATPases / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D013094:Spermatozoa / Q000187:drug effects / Q000502:physiology*
D006540:Herbicides; D006180:Proton-Translocating ATPases; D001280:Atrazine