Respiratory complex III is required to maintain complex I in mammalian mitochondria
Respiratory complex III is required to maintain complex I in mammalian mitochondria
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DOI：
10.1016/s1097-2765(04)00124-8
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发表时间：
2004-03-26
期刊：
影响因子：
16
通讯作者：
Enríquez, JA
中科院分区：
文献类型：
--
作者：
Acín-Pérez, R;Bayona-Bafaluy, MP;Enríquez, JA
氧化磷酸化（OXPHOS）缺陷患者中令人困惑的观察结果是，仅在一个蛋白质编码基因中存在与遗传改变相关的组合酶复合物缺陷。特别是，线粒体DNA编码的细胞色素B基因的突变与复合物I+III缺乏或仅与复合物III缺乏有关。我们已经复制了小鼠和人类培养的细胞模型窝藏细胞色素B突变相结合的复合物I-III缺陷。在这两种情况下，复合物III的组装受到阻碍，并导致复合物1的量严重减少，当复合物III的活性受到抑制时没有观察到。小鼠细胞中的代谢标记显示，复合物I组装，但其稳定性受到严重阻碍。相反，复合物III的稳定性不受复合物I的不存在的影响。复合物I和III之间的这种结构依赖性在一名携带无义细胞色素B突变的患者的肌肉活检中得到证实。
A puzzling observation in patients with oxidative phosphorylation (OXPHOS) deficiencies is the presence of combined enzyme complex defects associated with a genetic alteration in only one protein-coding gene. In particular, mutations in the mtDNA encoded cytochrome b gene are associated either with combined complex I+III deficiency or with only complex III deficiency. We have reproduced the combined complex I III defect in mouse and human cultured cell models harboring cytochrome b mutations. In both, complex III assembly is impeded and causes a severe reduction in the amount of complex 1, not observed when complex III activity was pharmacologically inhibited. Metabolic labeling in mouse cells revealed that complex I was assembled, although its stability was severely hampered. Conversely, complex III stability was not influenced by the absence of complex I. This structural dependence among complexes I and III was confirmed in a muscle biopsy of a patient harboring a nonsense cytochrome b mutation.