MOLECULAR REMEDY OF MITOCHONDRIAL DEFECTS

描述：近年来的研究表明，结构性和 线粒体质子转运NADH-泛醌功能缺陷 氧化还原酶（复合物I）参与许多人类疾病。 这些 疾病包括利伯氏遗传性视神经病变、帕金森氏症 疾病，肌张力障碍，严重乳酸酸中毒，各种形式的 脑肌病，可能还有亨廷顿氏病。 功能障碍 复合体I提出了三个问题：（1）损害的能力， 呼吸链将NADH氧化回所需的NAD 4， 其他的东西，用于柠檬酸循环和脂肪酸的操作 氧化酶 (2)这种酶泵送的能力受损 质子，导致ATP合成速率降低。 （三） 产生超氧自由基，导致线粒体DNA（mtDNA） 突变、脂质过氧化和蛋白质变性。 哺乳动物复合体I由至少41个不同的亚基组成， 膜结合酶复合物中最复杂的结构。 在这些亚基中，有七个由mtDNA编码，并在线粒体内合成。 cytoribosomal产物。 目前， 由MtDNA编码的亚基的突变和缺失不是 可校正的，以及由核ONA编码的多个亚基的突变 （nDNA）很难修复。 这笔赠款的总体目标是 应用是为了找到一种治疗疾病的方法， 复合体I功能障碍。

DESCRIPTION: It has been shown in recent years that structural and functional defects of mitochondrial proton-translocating NADH-ubiquinone oxidoreductase (complex I) are involved in many human diseases. These diseases include Leber's hereditary optic neuropathy, Parkinson's disease, dystonia, severe lactic acidosis, various forms of encephalomyopathies, and possibly Huntington's disease. Dysfunction of complex I presents three problems: (1) Impairment of the ability of the respiratory chain to oxidize NADH back to NAD4 which is required, among other things, for operation of the citric acid cycle and fatty acid oxidation enzymes. (2) Impairment of the ability of this enzyme to pump protons, resulting in a decrease in the rate of ATP synthesis. (3) Production of superoxide radicals, causing mitochondrial DNA (mtDNA) mutation, lipid peroxidation, and protein denaturation. Mammalian complex I is composed of at least 41 unlike subunits and has the most intricate structure among the membrane-bound enzyme complexes. Of these subunits, seven are encoded by mtDNA and synthesized within the mitochondrion, and other are cytoribosomal products. At present, mutations and deletions of the subunits encoded by MtDNA are not correctable, and mutations of plural subunits encoded by nuclear ONA (nDNA) are difficult to repair. The overall goal of this grant application is to find a remedy for the diseases that result from dysfunction of complex I.