Evaluation of pathogenic mechanisms involved in nuclear and mitochondrial DNA-encoded mitochondrial disorders

线粒体为细胞提供能量。线粒体功能紊乱可引起人类疾病。这些疾病被称为线粒体疾病。线粒体疾病通常涉及多个组织，特别是肌肉和大脑。这些疾病通常是由两种不同类型的DNA突变引起的；核和线粒体DNA。线粒体疾病有很多种形式；有些会影响幼儿或婴儿，有些会导致成人疾病。在某些情况下，遗传缺陷可能导致同样的疾病，而其他突变可能导致各种各样的症状。发生这种情况的原因尚不清楚。这项研究调查了几个因素，这些因素可能决定了为什么一些突变会导致某种疾病，而为什么其他突变会导致不同的疾病。这些因素包括突变细胞产生的能量水平的变化，以及突变细胞可能具有的诱导细胞死亡的不同程度的脆弱性。本提案的目标是确定导致突变引起不同临床症状的因素，总体目标是设计这些慢性疾病的治疗方法。

Mitochondria produce energy for the cell. Disorders of mitochondrial function can cause human disease. These diseases are referred to as the mitochondrial disorders. Mitochondrial disorders usually involve multiple tissues, particularly the muscle and brain.These disorders are usually caused by mutations in two different types of DNA; nuclear and mitochondrial DNA. There are many forms of mitochondrial disorders; some affect young children or infants and others cause adult disease. In some cases, genetic defects may cause the same disease and other mutations may cause a wide range of symptoms. The reason why this occurs is unknown. This study investigates several factors that may determine why some mutations lead to a certain disease and why others may cause different diseases. These factors include the variation in energy levels that are produced by the mutant cells, and the different levels of vunerability that mutated cells may have to induced cell death. The goal of this proposal is to identify the factors that lead to mutations causing different clinical symptoms with the overall aim being to design treatment for these chronic diseases.