Maassen J A, Janssen G M C, Lemkes H H J P
Department of Molecular Cell Biology, Leiden University Medical Center, The Netherlands.
J Endocrinol Invest. 2002 May;25(5):477-84. doi: 10.1007/BF03344042.
This review discusses the current insight by which mutations in mitochondrial DNA (mtDNA) contribute to the development of particular disease states with emphasis on diabetes mellitus. Mitochondria are the power factories of the cells and produce ATP by oxidizing reducing equivalents via the respiratory chain. These reducing equivalents originate mainly from the citric acid cycle that also occurs within the mitochondria. Human mitochondria contain their own genetic material in the form of circular DNA that encodes for only a fraction of the mitochondrial components. The other mitochondrial components are nuclear encoded. Pathogenic mutations in mtDNA can affect the activity of the respiratory chain, thereby leading to the reduced generation of ATP. However, mitochondria not only produce ATP but they also regulate cytosolic concentrations of signaling molecules such as calcium and iron ions. The metabolic processes within mitochondria such as the citric acid cycle determine the concentration of metabolites that can also act as signalling molecules. Furthermore, the respiratory chain and mitochondrion-associated monoamine oxidase are major producers of reactive oxygen radicals. As a result, mutations in mtDNA can deregulate multiple processes within cells and the balance of this deregulation may contribute to the clinical phenotype.
本综述讨论了线粒体DNA（mtDNA）突变导致特定疾病状态发展的当前见解，重点是糖尿病。线粒体是细胞的动力工厂，通过呼吸链氧化还原当量来产生ATP。这些还原当量主要来自也在线粒体内发生的柠檬酸循环。人类线粒体以环状DNA的形式包含自己的遗传物质，该遗传物质仅编码线粒体成分的一小部分。其他线粒体成分由核基因编码。mtDNA中的致病突变可影响呼吸链的活性，从而导致ATP生成减少。然而，线粒体不仅产生ATP，还调节钙和铁离子等信号分子的胞质浓度。线粒体内的代谢过程，如柠檬酸循环，决定了也可作为信号分子的代谢物浓度。此外，呼吸链和线粒体相关单胺氧化酶是活性氧自由基的主要产生者。因此，mtDNA中的突变可使细胞内的多个过程失调，这种失调的平衡可能导致临床表型。
