Schon E A, Santra S, Pallotti F, Girvin M E
Columbia University College of Physicians and Surgeons, New York, NY, USA.
Semin Cell Dev Biol. 2001 Dec;12(6):441-8. doi: 10.1006/scdb.2001.0281.
Maternally inherited mutations in the mtDNA-encoded ATPase 6 subunit of complex V (ATP synthase) of the respiratory chain/oxidative phosphorylation system are responsible for a subgroup of severe and often-fatal disorders characterized predominantly by lesions in the brain, particularly in the striatum. These include NARP (neuropathy, ataxia, and retinitis pigmentosa), MILS (maternally inherited Leigh syndrome), and FBSN (familial bilateral striatal necrosis). Of the five known pathogenic mutations causing these disorders, four are located at two codons (156 and 217), each of which can suffer mutations converting a conserved leucine to either an arginine or a proline. Based on the accumulating data on both the structure of ATP synthase and the mechanism by which rotary catalysis couples proton flow to ATP synthesis, we propose a model that may help explain why mutations at codons 156 and 217 are pathogenic.
呼吸链/氧化磷酸化系统复合体V（ATP合酶）的线粒体DNA编码的ATPase 6亚基中的母系遗传突变，是导致一类严重且常致命疾病的原因，这些疾病主要特征为脑部病变，尤其是纹状体病变。这些疾病包括NARP（神经病变、共济失调和色素性视网膜炎）、MILS（母系遗传的Leigh综合征）和FBSN（家族性双侧纹状体坏死）。在导致这些疾病的五个已知致病突变中，四个位于两个密码子（156和217）处，每个密码子都可能发生突变，将保守的亮氨酸转换为精氨酸或脯氨酸。基于关于ATP合酶结构以及旋转催化将质子流与ATP合成偶联机制的累积数据，我们提出了一个模型，该模型可能有助于解释为什么密码子156和217处的突变具有致病性。
