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Glutathione S-transferase pi localizes in mitochondria and protects against oxidative stress.


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タイトル: Glutathione S-transferase pi localizes in mitochondria and protects against oxidative stress.
著者: Goto, Shinji / Kawakatsu, Miho / Izumi, Shin-Ichi / Urata, Yoshishige / Kageyama, Kan / Ihara, Yoshito / Koji, Takehiko / Kondo, Takahito
発行日: 2009年 5月15日
出版者: Elsevier Science Limited
引用: Free Radical Biology & Medicine, 46(10), pp.1392-1403; 2009
抄録: Glutathione S-transferases (GSTs) are multifunctional enzymes involved in the protection of cellular components against anti-cancer drugs or peroxidative stress. Previously we found that GST pi, an isoform of the GSTs, is transported into the nucleus. In the present study, we found that GST pi is present in mitochondria as well as in the cytosol and nucleus in mammalian cell lines. A construct comprising the 84 amino acid residues in the amino-terminal region of GST pi and green fluorescent protein was detected in the mitochondria. The mutation of arginine to alanine at positions 12, 14, 19, 71, and 75 in full-length GST pi completely abrogated the ability to distribute in the mitochondria, suggesting that arginine, a positively charged residue, is required for the mitochondrial transport of GST pi. Chemicals generating reactive oxygen species, such as rotenone and antimycin A, decreased cell viability and reduced mitochondrial membrane potential. The overexpression of GST pi diminished these changes. GST pi-targeting siRNA abolished the protective effect of GST pi on the mitochondria under oxidative stress. The findings indicate that the peptide signal is conducive to the mitochondrial localization of GST pi under steady-state conditions without alternative splicing or posttranslational modifications such as proteolysis, suggesting that GST pi protects mitochondria against oxidative stress.
キーワード: Glutathione S-transferase π / Mitochondria / Mitochondrial targeting signal / Rotenone / Antimycin A / Oxidative stress / Free radicals
URI: http://hdl.handle.net/10069/21933
ISSN: 08915849
DOI: 10.1016/j.freeradbiomed.2009.02.025
PubMed ID: 19269317
権利: Copyright (C) 2009 Elsevier Inc. All rights reserved.
資料タイプ: Journal Article
原稿種類: author
出現コレクション:115 学術雑誌論文

引用URI : http://hdl.handle.net/10069/21933

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