Department of Medical Biochemistry, Biology and Physics, University of Bari, P.zza G. Cesare, Policlinico, 70124, Bari, Italy.
J Bioenerg Biomembr. 2009 Dec;41(6):509-16. doi: 10.1007/s10863-009-9252-4.
A summary is presented of the cellular function and topology of the protein products of genes whose mutations are associated with familial forms of parkinsonism, with particular emphasis on mitochondrial involvement. Observations are reviewed which show mitochondrial respiratory depression in the fibroblasts of a patient affected by familial parkinsonism associated with homozygous PINK1 mutation. The respiratory depression, which was due to loss of mitochondrial cytochrome c, was associated with decreased capacity of respiratory chain oxidative phosphorylation and enhanced cellular level of ROS. Sequence analysis of the overall mtDNA revealed coexistence with the PINK1 mutation of homoplasmic point mutations in the ND5 and ND6 genes of complex I. The presence of these mutations appears to have an impact on the development of the parkinsonism, which can also occur in the heterozygous PINK1 mutation state.
本文总结了与家族性帕金森病相关基因突变的蛋白产物的细胞功能和拓扑结构，特别强调了线粒体的参与。本文回顾了一些观察结果，这些结果表明，在一位受家族性帕金森病影响的患者的成纤维细胞中存在线粒体呼吸抑制，该患者的 PINK1 基因突变呈纯合子状态。呼吸抑制是由于线粒体细胞色素 c 的丧失引起的，与呼吸链氧化磷酸化能力下降和细胞内 ROS 水平升高有关。对整个 mtDNA 的序列分析显示，在 PINK1 突变的同质性点突变与复合物 I 的 ND5 和 ND6 基因共存。这些突变的存在似乎对帕金森病的发展有影响，这种情况也可能发生在 PINK1 突变的杂合状态。
