期刊
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE
卷 1822, 期 8, 页码 1216-1222出版社
ELSEVIER SCIENCE BV
DOI: 10.1016/j.bbadis.2012.04.014
关键词
Leber's hereditary optic neuropathy; Oxidative phosphorylation; Mitochondrial DNA; Haplogroup; Cybrid
资金
- Instituto de Salud Carlos III [FIS-PI10/00662, PI08/0264, PI11/01301]
- Departamento de Ciencia, Tecnologia y Universidad del Gobierno de Aragon y Fondo Social Europeo [B33]
- Instituto Aragones de Ciencias de la Salud [PIPAMER10-010]
- Fundacion ARAID
- Asociacion de Enfermos de Patologia Mitocondrial (AEPMI)
Leber's hereditary optic neuropathy is a maternally inherited optic atrophy caused by mitochondrial DNA point mutations. Previous epidemiological studies have shown that individuals from mitochondrial genetic backgrounds (haplogroups) J/Uk and H have a higher and a lower risk, respectively, of suffering this disorder. To analyze the bases of these associations at cellular and molecular levels, functional studies with cybrids provide high quality evidence. Cybrids from haplogroup J contain less mitochondrial deoxyribonucleic acid (DNA) and ribonucleic acid (RNA) and synthesize a smaller amount of mitochondrial DNA-encoded polypeptides than those from haplogroup H. Haplogroup J cybrids also display lower oxygen consumption, mitochondrial inner membrane potential and total adenosine-5'-triphosphate (ATP) levels. Moreover, mitochondrial DNA levels correlate with many parameters of the oxidative phosphorylation system. These results suggest that the mitochondria! DNA amount determines oxidative phosphorylation capacity and, along with other recently published observations, support the possibility that mitochondrial DNA levels may be responsible for the bias of the disorder toward males, for the incomplete penetrance of mutations causing Leber's hereditary optic neuropathy and for the association of the disease with particular mitochondria! DNA haplogroups. (C) 2012 Elsevier B.V. All rights reserved.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据