Pathogenesis of primary defects in mitochondrial ATP synthesis

被引:95
作者
Schon, EA
Santra, S
Pallotti, F
Girvin, ME
机构
[1] Columbia Univ Coll Phys & Surg, New York, NY 10032 USA
[2] Albert Einstein Coll Med, New York, NY USA
关键词
ATPase; 6; complex V; disease; FBSN; MILS; mtDNA; NARP; rotary catalysis;
D O I
10.1006/scdb.2001.0281
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
Maternally inherited mutations in the mtDNA-encoded ATPase 6 subunit of complex V (ATP synthase) of the respirators 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.
引用
收藏
页码:441 / 448
页数:8
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