VDAC1 is a transplasma membrane NADH-ferricyanide reductase
VDAC1 is a transplasma membrane NADH-ferricyanide reductase
复制标题
DOI：
10.1074/jbc.m311020200
复制
发表时间：
2004-02-06
影响因子：
4.8
通讯作者：
Lawen, A
中科院分区：
文献类型：
--
作者：
Baker, MA;Lane, DJR;Lawen, A
孔蛋白亚型1或VDAC（电压依赖性阴离子选择性通道）1是线粒体外膜中的主要蛋白质。我们以前证明了质膜NADH-铁氰化物还原酶活性在线粒体扰动后上调，因此表明它作为细胞氧化还原传感器发挥作用。已知VDAC 1在质膜中表达;然而，它在那里的功能仍然是一个谜。在这里，我们表明，VDAC 1，当在质膜上表达，作为一个NADH-铁氰化物还原酶的功能。从质膜和线粒体组分中纯化的VDAC 1制剂显示出NADH-铁氰化物还原酶活性，可以用针对VDAC的多克隆抗体和单克隆抗体进行免疫沉淀（1）。用携带N-末端信号肽的pl-VDAC 1-GFP转染细胞，将VDAC 1引导至质膜，如通过共聚焦显微镜和FAGS分析所示，并显著增加转染细胞的质膜NADH-铁氰化物还原酶活性。众所周知的VDAC 1分子的这种新的酶活性可能为其在质膜中的作用提供了解释。我们的数据表明，VDAC 1在质膜中的主要功能是NADH（铁氰化物）还原酶，可能参与维持细胞氧化还原稳态。
Porin isoform 1 or VDAC (voltage-dependent anion-selective channel) 1 is the predominant protein in the outer mitochondrial membrane. We demonstrated previously that a plasma membrane NADH-ferricyanide reductase activity becomes up-regulated upon mitochondrial perturbation, and therefore suggested that it functions as a cellular redox sensor. VDAC1 is known to be expressed in the plasma membrane; however, its function there remained a mystery. Here we show that VDAC1, when expressed in the plasma membrane, functions as a NADH-ferricyanide reductase. VDAC1 preparations purified from both plasma membrane and mitochondria fractions exhibit NADH-ferricyanide reductase activity, which can be immunoprecipitated with poly- and monoclonal antibodies directed against VDAC(1). Transfecting cells with pl-VDAC1-GFP, which carries an N-terminal signal peptide, directs VDAC1 to the plasma membrane, as shown by confocal microscopy and FAGS analysis, and significantly increases the plasma membrane NADH-ferricyanide reductase activity of the transfected cells. This novel enzymatic activity of the well known VDAC1 molecule may provide an explanation for its role in the plasma membrane. Our data suggest that a major function of VDAC1 in the plasma membrane is that of a NADH(-ferricyanide) reductase that may be involved in the maintenance of cellular redox homeostasis.