New Control Mechanism for Protein Transport in Cells

线粒体外膜细胞色素B（OM B）是在大鼠肝脏中发现的微粒体细胞色素b_5（b_5）的同系物。OMb与细胞色素P-450_<17 α>共定位于Leydig细胞，而b_5则未检测到。我们已经证明，在生理量的P-450还原酶的作用下，OMb刺激17 α-羟化酶和P-45O_<17 α>的裂解酶反应，导致孕酮合成雄烯二酮的增加。因此，OM带而不是b_5被认为是激活的原因，被确定为大鼠睾丸雄激素生成的调节剂。这一发现促使我们研究OMb的新生理功能。用免疫组织化学方法分析了OMb、b_5和P-45 O_（17 α）在大鼠脑内的组织定位。在肾上腺皮质中，OMb和b_5分别主要分布于皮质的外侧和内侧。在小脑中，OMb和P-450_<17 α>仅在浦肯野细胞中检测到并共定位，浦肯野细胞是神经类固醇生成的主要部位。在大脑中，它们共同定位于产生脑脊液的脉络丛室管膜细胞中。OMb也存在于海马和神经节层。而b_5在脑内几乎未被观察到。部分纯化的浦肯野细胞从孕酮转化为睾酮，表明P-450 <17 α>和17 β-羟基类固醇脱氢酶在转化过程中均具有活性，并提示OMb可能是刺激细胞内P-450 <17 α>催化反应的原因。这些结果表明，OMb不仅在普通的内分泌系统，而且在更高的生命活动中的重要功能。

Outer mitochondrial membrane cytochrome b (OMb) was discovered in rat liver as a homologue of microsomal cytochrome b_5 (b_5). OMb was co-localized in Leydig cells with cytochrome P-450_<17α>, which catalyzes androgengenesis therein, whereas b_5 was undetectable. We have demonstrated that OMb stimulates the 17α-hydroxylase and lyase reactions of P-45O_<17α> under limited but physiological amounts of P-450 reductase, leading to an enhanced production of androstenedione from progesterone. Thus, OMband not b_5, which was believed to be responsible for the activation, was identified as a modulator for androgengenesis in rat testes. This finding prompted us to study the novel physiological functions of OMb. We analyzed the tissue localization of OMb, b_5 and P-45O_<17α> in rats by immunohistochemical staining. In the adrenal cortex OMb and b_5 were mainly present in the outer and inner portions, respectively. In the cerebellum OMb and P-450_<17α> were only detected and co-localized in the Purkinje cell, a major site for neurosteroidogenesis. In cerebrum they were co-localized in the ependymal cells of choroid plexus, which produces the cerebrospinal fluid. OMb was present also in the hippocampus and ganglionic layer. In contrast, b_5 was scarcely observed in the brain. Partially purified Purkinje cells produced testosterone from progesterone, indicating that both P-450_<17α> and 17β-hydroxysteroid dehydrogenase were active in the conversion and suggested that OMb could be responsible for stimulation of P-450_<17α>-catalyzed reactions in the cells. These results imply important functions of OMb in not only ordinary endocrine systems but also in higher life activities.