散发性肌萎缩侧索硬化症中的线粒体

Mitochondria in sporadic amyotrophic lateral sclerosis.

作者信息

Swerdlow R H, Parks J K, Cassarino D S, Trimmer P A, Miller S W, Maguire D J, Sheehan J P, Maguire R S, Pattee G, Juel V C, Phillips L H, Tuttle J B, Bennett J P, Davis R E, Parker W D

机构信息

Department of Neurology, University of Virginia Health Sciences Center, 1 Hospital Drive, Charlottesville, Virginia 22908, USA.

出版信息

Exp Neurol. 1998 Sep;153(1):135-42. doi: 10.1006/exnr.1998.6866.

DOI:10.1006/exnr.1998.6866

PMID:9743575

Abstract

Mitochondria are abnormal in persons with amyotrophic lateral sclerosis (ALS) for unknown reasons. We explored whether aberration of mitochondrial DNA (mtDNA) could play a role in this by transferring mitochondrial DNA (mtDNA) from ALS subjects to mtDNA-depleted human neuroblastoma cells. Resulting ALS cytoplasmic hybrids (cybrids) exhibited abnormal electron transport chain functioning, increases in free radical scavenging enzyme activities, perturbed calcium homeostasis, and altered mitochondrial ultrastructure. Recapitulation of defects previously observed in ALS subjects and ALS transgenic mice by expression of ALS mtDNA support a pathophysiologic role for mtDNA mutation in some persons with this disease.

摘要

肌萎缩侧索硬化症（ALS）患者的线粒体出于未知原因出现异常。我们通过将ALS患者的线粒体DNA（mtDNA）转移到线粒体DNA缺失的人神经母细胞瘤细胞中，探究线粒体DNA（mtDNA）的畸变是否在此过程中发挥作用。由此产生的ALS细胞质杂种细胞（cybrids）表现出异常的电子传递链功能、自由基清除酶活性增加、钙稳态紊乱以及线粒体超微结构改变。通过表达ALS mtDNA重现先前在ALS患者和ALS转基因小鼠中观察到的缺陷，支持了mtDNA突变在部分该疾病患者中的病理生理作用。