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Mitochondrial translocation of cofilin is required for allyl isothiocyanate-mediated cell death via ROCK1/PTEN/PI3K

Guo-bing Li1, Qi Cheng, Lei Liu

  • 1Department of Pharmacognosy, College of Pharmacy, 3rd Military Medical University, Chongqing 400038, China.

Cell Communication and Signaling : CCS
|July 31, 2013
PubMed
Abstract

Insights

Allyl isothiocyanate (AITC) triggers apoptosis by dephosphorylating cofilin, promoting its mitochondrial translocation. This process, involving the ROCK1/PTEN/PI3K pathway, leads to cell death and inhibits tumor growth.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Biochemistry

Background:

  • Cofilin, an actin depolymerizing factor (ADF)/cofilin family member, regulates actin dynamics.
  • Mitochondrial translocation of cofilin is crucial for apoptosis regulation.

Purpose of the Study:

  • To investigate the mechanism of allyl isothiocyanate (AITC)-induced apoptosis.
  • To elucidate the role of cofilin dephosphorylation and mitochondrial translocation in AITC-mediated cell death.

Main Methods:

  • Analysis of actin polymerization (F-actin and G-actin).
  • Assessment of cofilin phosphorylation status and mitochondrial translocation.
  • Investigation of the ROCK1/PTEN/PI3K signaling pathway.
  • In vivo studies using a mouse leukemia xenograft model.

Main Results:

  • AITC induces mitochondrial injury and apoptosis, associated with altered actin polymerization.
  • AITC activates protein phosphatases PP1 and PP2A, leading to cofilin dephosphorylation.
  • Dephosphorylated cofilin binds to G-actin and translocates to mitochondria.
  • Inhibition of the ROCK1/PTEN/PI3K pathway is critical for AITC-induced cofilin dephosphorylation and mitochondrial translocation.
  • AITC inhibits tumor growth in vivo, correlating with cofilin dephosphorylation.

Conclusions:

  • AITC-induced apoptosis involves activation of ROCK1 and PTEN, and inactivation of PI3K.
  • This signaling cascade activates PP1 and PP2A, resulting in cofilin dephosphorylation.
  • Dephosphorylated cofilin binds G-actin, translocates to mitochondria, causing dysfunction and apoptosis.
  • The findings elucidate a novel mechanism for AITC-induced cell death and potential anti-cancer effects.

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