影响氧化磷酸化的线粒体DNA和核突变：将临床缺陷的严重程度与生物能量受损程度相关联。

MtDNA and nuclear mutations affecting oxidative phosphorylation: correlating severity of clinical defect with extent of bioenergetic compromise.

作者信息

Robinson B H

机构信息

Department of Biochemistry, University of Toronto, Ontario, Canada.

出版信息

J Bioenerg Biomembr. 1994 Jun;26(3):311-6. doi: 10.1007/BF00763102.

DOI:10.1007/BF00763102

PMID:8077184

Abstract

Rates of ATP synthesis were studied in cultured skin fibroblasts treated with digitonin. In fibroblasts from patients with complex I deficiency, complex IV and complex V deficiency rates of ATP synthesis were decreased below the levels found in controls. In mitochondria isolated from cultured lymphoblasts, ATP synthesis was also decreased by 35-50% in cases of Leigh's disease due to complex I, complex IV, or complex V deficiency. Calculating the effect of the mutations in the various complexes on the overall efficiency of oxidative phosphorylation, we show that the mtDNA 8993 mutation which affects the activity of the F1F0 ATPase (complex V) has the strongest effect.

摘要

研究了用洋地黄皂苷处理的培养皮肤成纤维细胞中的ATP合成速率。在患有复合体I缺陷、复合体IV和复合体V缺陷的患者的成纤维细胞中，ATP合成速率低于对照组的水平。在从培养的淋巴细胞中分离出的线粒体中，由于复合体I、复合体IV或复合体V缺陷导致的Leigh病患者，ATP合成也减少了35 - 50%。通过计算各种复合体中的突变对氧化磷酸化总体效率的影响，我们发现影响F1F0 ATP酶（复合体V）活性的线粒体DNA 8993突变具有最强的影响。