MODELS FOR NUCLEAR EXPRESSION OF MITOCHONDRIAL GENES

越来越多的患者被确认患有线粒体疾病。这些疾病在临床症状和形态生化特征上表现出极大的多样性。虽然在许多患者中发现了mtDNA突变，但目前还没有有效的治疗方法。一种极有可能克服mtdna编码蛋白突变的方法是在细胞核中放置受影响基因的野生型拷贝，并将表达的蛋白靶向线粒体，以代替有缺陷的线粒体蛋白发挥作用。人类mtDNA编码的所有蛋白质都是疏水的，位于线粒体内膜，并具有多个跨膜区域。有人提出，这些基因保留在mtDNA中的原因之一是它们编码的蛋白质过于疏水，无法在细胞核中表达并转运到线粒体中。莱茵衣藻（Chlamydomonas reinhardtii）和多毛藻（Polytomella spp）在其核DNA中编码有几个特定的呼吸链亚基基因，而在人类中则编码在mtDNA中。这些藻类将用于研究呼吸链亚基基因从mtDNA转移到细胞核的过程。mtDNA和几个核dna编码的呼吸链复合体亚基的基因序列将被确定和分析。鉴定这些多肽的结构特征对它们进入线粒体很重要，应该适用于开发由mtdna编码的多肽基因突变引起的人类疾病的遗传疗法。

Increasing numbers of patients are being identified as suffering from mitochondrial diseases. Such diseases display great diversity in clinical symptoms and morphological and biochemical characteristics. Although mtDNA mutations have been identified in many patients, there are presently no effective treatments. One method which has great potential for overcoming mutations in mtDNA-encoded proteins is to place a wild-type copy of the affected gene in the nucleus, and target the expressed protein to the mitochondrion to function in place of the defective mitochondrial protein. All proteins encoded in human mtDNA are hydrophobic, are located in the mitochondrial inner membrane, and have multiple membrane-spanning regions. It has been proposed that one of the reasons that these genes have been retained in mtDNA is that the proteins they encode are too hydrophobic to be expressed in the nucleus and transported into mitochondria. The Chlorophytic algae Chlamydomonas reinhardtii and Polytomella spp. Have several specific respiratory chain subunit genes encoded in their nuclear DNA, that in humans are encoded in the mtDNA. These algae will be used to study the transfer of genes of the respiratory chain subunits from the mtDNA to the nucleus. The sequences of the mtDNA and of genes for several nuclear DNA-encoded respiratory chain complex subunits will be determined and analyzed. The identification of structural features of these polypeptides that are important for their import into mitochondria should be applicable towards the development of genetic therapies for human diseases resulting from mutations in mtDNA-encoded polypeptide genes.