Mitochondrial targeting of mouse NQO1 and CYP1B1 proteins.

Mitochondrial targeting of mouse NQO1 and CYP1B1 proteins.
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DOI:
10.1016/j.bbrc.2013.05.051
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发表时间:
2013-06-14
影响因子:
3.1
通讯作者:
Nebert, Daniel W.
Nebert, Daniel W.
中科院分区:
生物学4区
文献类型:
--
作者:
Dong, Hongbin;Shertzer, Howard G.;Genter, Mary Beth;Gonzalez, Frank J.;Vasiliou, Vasilis;Jefcoate, Colin;Nebert, Daniel W.

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四种二恶英诱导酶- nad (P)H:醌氧化还原酶-1 (NQO1)和三种细胞色素P450 (CYP1A1, CYP1A2和CYP1B1) -参与各种内源性和外源性药物的解毒和代谢激活。NQO1通常被认为是一种胞质酶;CYP1蛋白主要位于内质网(ER),而CYP1A1和CYP1A2蛋白也靶向线粒体。该实验室已经产生了Cyp1a1(mc/mc)和Cyp1a1(mtt/mtt)敲入小鼠系,其中Cyp1a1蛋白分别专门针对ER(微粒体)和线粒体。比较二恶英处理的Cyp1(+/+)野生型、Cyp1a1(mc/mc)、Cyp1a1(mtt/mtt)和Cyp1a1(−/−)、Cyp1b1(−/−)和Nqo1(−/−)敲除小鼠,在本研究中,我们发现[a] Nqo1蛋白定位于细胞质、内质网和线粒体,[b] Cyp1b1蛋白(类似于Cyp1a1和CYP1A2蛋白)转运到线粒体和内质网,[c] Nqo1和Cyp1b1靶向线粒体或内质网膜,不依赖于Cyp1a1在细胞膜上的存在。
Four dioxin-inducible enzymes—NAD(P)H:quinone oxidoreductase-1 (NQO1) and three cytochromes P450 (CYP1A1, CYP1A2 & CYP1B1)—are implicated in both detoxication and metabolic activation of various endobiotics and xenobiotics. NQO1 is generally regarded as a cytosolic enzyme; whereas CYP1 proteins are located primarily in endoplasmic reticulum (ER), CYP1A1 and CYP1A2 proteins are also targeted to mitochondria. This lab has generated Cyp1a1(mc/mc) and Cyp1a1(mtt/mtt) knock-in mouse lines in which CYP1A1 protein is targeted exclusively to ER (microsomes) and mitochondria, respectively. Comparing dioxin-treated Cyp1(+/+) wild-type, Cyp1a1(mc/mc), Cyp1a1(mtt/mtt), and Cyp1a1(−/−), Cyp1b1(−/−) and Nqo1(−/−) knockout mice, in the present study we show that [a] NQO1 protein locates to cytosol, ER and mitochondria, [b] CYP1B1 protein (similar to CYP1A1 and CYP1A2 proteins) traffics to mitochondria as well as ER, and [c] NQO1 and CYP1B1 targeting to mitochondrial or ER membranes is independent of CYP1A1 presence in that membrane.
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发表时间: 2010-01
影响因子: 2.3
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