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、形态和生化特征上表现出很大的多样性。虽然已经在许多患者中发现了线粒体DNA突变，但目前还没有有效的治疗方法。一种有巨大潜力克服mtDNA编码蛋白突变的方法是将受影响基因的野生型副本放置在细胞核中，并将表达的蛋白靶向线粒体，以取代缺陷的线粒体蛋白发挥功能。人类线粒体DNA中编码的所有蛋白质都是疏水性的，位于线粒体内膜，并具有多个跨膜区域。有人提出，这些基因保留在线粒体DNA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运输到线粒体中。绿藻、莱茵衣藻和多毛藻。有几个特定的呼吸链亚单位基因编码在他们的核DNA中，在人类中是在线粒体DNA中编码的。这些藻类将被用来研究呼吸链亚单位的基因从线粒体DNA到细胞核的转移。线粒体DNA和几个核DNA编码的呼吸链复合体亚单位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是重要的，这将适用于开发由mtDNA编码的多肽基因突变引起的人类疾病的遗传治疗。

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.