Mitochondrial functions and estrogen receptor-dependent nuclear translocation of pleiotropic human prohibitin 2
Mitochondrial functions and estrogen receptor-dependent nuclear translocation of pleiotropic human prohibitin 2
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DOI：
10.1074/jbc.m605260200
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发表时间：
2006-11-24
影响因子：
4.8
通讯作者：
Endo, Hitoshi
中科院分区：
文献类型：
--
作者：
Kasashima, Katsumi;Ohta, Eriko;Endo, Hitoshi
具有多种细胞功能的蛋白质为真核细胞提供了生物多样性。在当前的研究中，我们确定了人类抑制素2（PHB2）的线粒体功能，它最初被鉴定为雌激素依赖性转录活性的抑制因子。PHB2的线粒体复合物由PHB1、电压依赖性阴离子通道2、腺嘌呤核苷酸转位酶2以及抗凋亡的Hax - 1组成，Hax - 1是PHB2的一种新型结合伴侣。在HeLa细胞中，通过RNA干扰介导的PHB2敲低，由于Hax - 1的下调和线粒体的碎片化，导致了半胱天冬酶依赖性凋亡。我们还发现，尽管PHB2主要在HeLa细胞的线粒体中表达，但在雌激素受体α和雌二醇存在的情况下，它会转移到细胞核。在此，我们首先证明了哺乳动物PHB2在线粒体中的作用以及其核靶向的分子机制，并表明PHB2是一种可能直接偶联核 - 线粒体相互作用的分子。
Proteins with multiple cellular functions provide biological diversity to eukaryotic cells. In the current studies, we identified the mitochondrial functions of human prohibitin 2 (PHB2), which was initially identified as a repressor of estrogen-dependent transcriptional activity. The mitochondrial complex of PHB2 consists of PHB1, voltage-dependent anion channel 2, adenine nucleotide translocator 2, and the anti-apoptotic Hax-1, which is a novel binding partner for PHB2. RNA interference-mediated knockdown of PHB2 in HeLa cells resulted in caspase-dependent apoptosis through down-regulation of Hax-1 and fragmentation of mitochondria. We also found that, although PHB2 is predominantly expressed in the mitochondria of HeLa cells, it translocates to nucleus in the presence of estrogen receptor alpha and estradiol. Here, we first demonstrated the roles of mammalian PHB2 in mitochondria and the molecular mechanism of its nuclear targeting and showed that PHB2 is a possible molecule directly coupling nuclear-mitochondrial interaction.