Mitochondrial translocation and interaction of cofilin and Drp1 are required for erucin-induced mitochondrial fission and apoptosis

Cofilin is a member of the actin-depolymerizing factor (ADF) family protein, which plays an essential role in regulation of the mitochondrial apoptosis. It remains unclear how cofilin regulates the mitochondrial apoptosis. Here, we report for the first time that natural compound 4-methylthiobutyl is...

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Main Authors:	Li, Guobing, Zhou, Jing, Budhraja, Amit, Hu, Xiaoye, Chen, Yibiao, Cheng, Qi, Liu, Lei, Zhou, Ting, Li, Ping, Liu, Ehu, Gao, Ning
Format:	Online
Language:	English
Published:	Impact Journals LLC 2014
Online Access:	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4359335/

id	pubmed-4359335
recordtype	oai_dc
spelling	pubmed-43593352015-03-26 Mitochondrial translocation and interaction of cofilin and Drp1 are required for erucin-induced mitochondrial fission and apoptosis Li, Guobing Zhou, Jing Budhraja, Amit Hu, Xiaoye Chen, Yibiao Cheng, Qi Liu, Lei Zhou, Ting Li, Ping Liu, Ehu Gao, Ning Research Paper Cofilin is a member of the actin-depolymerizing factor (ADF) family protein, which plays an essential role in regulation of the mitochondrial apoptosis. It remains unclear how cofilin regulates the mitochondrial apoptosis. Here, we report for the first time that natural compound 4-methylthiobutyl isothiocyanate (erucin) found in consumable cruciferous vegetables induces mitochondrial fission and apoptosis in human breast cancer cells through the mitochondrial translocation of cofilin. Importantly, cofilin regulates erucin-induced mitochondrial fission by interacting with dynamin-related protein (Drp1). Knockdown of cofilin or Drp1 markedly reduced erucin-mediated mitochondrial translocation and interaction of cofilin and Drp1, mitochondrial fission, and apoptosis. Only dephosphorylated cofilin (Ser 3) and Drp1 (Ser 637) are translocated to the mitochondria. Cofilin S3E and Drp1 S637D mutants, which mimick the phosphorylated forms, suppressed mitochondrial translocation, fission, and apoptosis. Moreover, both dephosphorylation and mitochondrial translocation of cofilin and Drp1 are dependent on ROCK1 activation. In vivo findings confirmed that erucin-mediated inhibition of tumor growth in a breast cancer cell xenograft mouse model is associated with the mitochondrial translocation of cofilin and Drp1, fission and apoptosis. Our study reveals a novel role of cofilin in regulation of mitochondrial fission and suggests erucin as a potential drug for treatment of breast cancer. Impact Journals LLC 2014-12-16 /pmc/articles/PMC4359335/ /pubmed/25595902 Text en Copyright: © 2015 Li et al. http://creativecommons.org/licenses/by/2.5/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited
repository_type	Open Access Journal
institution_category	Foreign Institution
institution	US National Center for Biotechnology Information
building	NCBI PubMed
collection	Online Access
language	English
format	Online
author	Li, Guobing Zhou, Jing Budhraja, Amit Hu, Xiaoye Chen, Yibiao Cheng, Qi Liu, Lei Zhou, Ting Li, Ping Liu, Ehu Gao, Ning
spellingShingle	Li, Guobing Zhou, Jing Budhraja, Amit Hu, Xiaoye Chen, Yibiao Cheng, Qi Liu, Lei Zhou, Ting Li, Ping Liu, Ehu Gao, Ning Mitochondrial translocation and interaction of cofilin and Drp1 are required for erucin-induced mitochondrial fission and apoptosis
author_facet	Li, Guobing Zhou, Jing Budhraja, Amit Hu, Xiaoye Chen, Yibiao Cheng, Qi Liu, Lei Zhou, Ting Li, Ping Liu, Ehu Gao, Ning
author_sort	Li, Guobing
title	Mitochondrial translocation and interaction of cofilin and Drp1 are required for erucin-induced mitochondrial fission and apoptosis
title_short	Mitochondrial translocation and interaction of cofilin and Drp1 are required for erucin-induced mitochondrial fission and apoptosis
title_full	Mitochondrial translocation and interaction of cofilin and Drp1 are required for erucin-induced mitochondrial fission and apoptosis
title_fullStr	Mitochondrial translocation and interaction of cofilin and Drp1 are required for erucin-induced mitochondrial fission and apoptosis
title_full_unstemmed	Mitochondrial translocation and interaction of cofilin and Drp1 are required for erucin-induced mitochondrial fission and apoptosis
title_sort	mitochondrial translocation and interaction of cofilin and drp1 are required for erucin-induced mitochondrial fission and apoptosis
description	Cofilin is a member of the actin-depolymerizing factor (ADF) family protein, which plays an essential role in regulation of the mitochondrial apoptosis. It remains unclear how cofilin regulates the mitochondrial apoptosis. Here, we report for the first time that natural compound 4-methylthiobutyl isothiocyanate (erucin) found in consumable cruciferous vegetables induces mitochondrial fission and apoptosis in human breast cancer cells through the mitochondrial translocation of cofilin. Importantly, cofilin regulates erucin-induced mitochondrial fission by interacting with dynamin-related protein (Drp1). Knockdown of cofilin or Drp1 markedly reduced erucin-mediated mitochondrial translocation and interaction of cofilin and Drp1, mitochondrial fission, and apoptosis. Only dephosphorylated cofilin (Ser 3) and Drp1 (Ser 637) are translocated to the mitochondria. Cofilin S3E and Drp1 S637D mutants, which mimick the phosphorylated forms, suppressed mitochondrial translocation, fission, and apoptosis. Moreover, both dephosphorylation and mitochondrial translocation of cofilin and Drp1 are dependent on ROCK1 activation. In vivo findings confirmed that erucin-mediated inhibition of tumor growth in a breast cancer cell xenograft mouse model is associated with the mitochondrial translocation of cofilin and Drp1, fission and apoptosis. Our study reveals a novel role of cofilin in regulation of mitochondrial fission and suggests erucin as a potential drug for treatment of breast cancer.
publisher	Impact Journals LLC
publishDate	2014
url	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4359335/
_version_	1613198531043000320

Mitochondrial translocation and interaction of cofilin and Drp1 are required for erucin-induced mitochondrial fission and apoptosis

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