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Korean Society for Biochemistry and Molecular Biology (생화학분자생물학회)
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Niclosamide induces mitochondria fragmentation and promotes both apoptotic and autophagic cell death

  • Park, So-Jung (Graduate School of East-West Medical Science, Kyung Hee University) ;
  • Shin, Ji-Hyun (Graduate School of East-West Medical Science, Kyung Hee University) ;
  • Kang, Hee (Graduate School of East-West Medical Science, Kyung Hee University) ;
  • Hwang, Jung-Jin (Institute for Innovative Cancer Research, Asan Medical Center) ;
  • Cho, Dong-Hyung (Graduate School of East-West Medical Science, Kyung Hee University)
  • Received : 2011.04.25
  • Accepted : 2011.06.03
  • Published : 2011.08.31
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Abstract

Mitochondrial dynamics not only involves mitochondrial morphology but also mitochondrial biogenesis, mitochondrial distribution, and cell death. To identify specific regulators to mitochondria dynamics, we screened a chemical library and identified niclosamide as a potent inducer of mitochondria fission. Niclosamide promoted mitochondrial fragmentation but this was blocked by down-regulation of Drp1. Niclosamide treatment resulted in the disruption of mitochondria membrane potential and reduction of ATP levels. Moreover, niclosamide led to apoptotic cell death by caspase-3 activation. Interestingly, niclosamide also increased autophagic activity. Inhibition of autophagy suppressed niclosamide-induced cell death. Therefore, our findings suggest that niclosamide induces mitochondria fragmentation and may contribute to apoptotic and autophagic cell death.

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References

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