Cytochrome c oxidase is required for the assembly/stability of respiratory complex I in mouse fibroblasts
Cytochrome c oxidase is required for the assembly/stability of respiratory complex I in mouse fibroblasts
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DOI：
10.1128/mcb.01767-05
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发表时间：
2006-07-01
影响因子：
5.3
通讯作者：
Moraes, Carlos T.
中科院分区：
文献类型：
--
作者：
Diaz, Francisca;Fukui, Hirokazu;Moraes, Carlos T.
细胞色素c氧化酶(COX)的生物发生需要COX10，它编码一种原血红素：参与血红素a生物合成的血红素O法尼基转移酶。我们创造了COX10基因敲除的小鼠细胞，这种细胞缺乏细胞色素AA(3)，呼吸困难，没有可检测到的复合体IV活性，不能组装COX。出乎意料的是，在COX10基因敲除克隆中，呼吸复合体I的水平显著降低。COX的药理抑制不影响复合体I的水平，转导表达野生型或突变型COX10(保留残留活性)的慢病毒敲除细胞使复合体I恢复到正常水平。脉冲追逐实验未能检测到新组装的复合体I，这表明要么COX是组装复合体I所必需的，要么后者被迅速降解。这些结果表明，在快速分裂的细胞中，复合体IV对于复合体I的组装或稳定性是必需的。
Cytochrome c oxidase (COX) biogenesis requires COX10, which encodes a protoheme:heme O farnesyl transferase that participates in the biosynthesis of heme a. We created COX10 knockout mouse cells that lacked cytochrome aa(3), were respiratory deficient, had no detectable complex IV activity, and were unable to assemble COX. Unexpectedly, the levels of respiratory complex I were markedly reduced in COX10 knockout clones. Pharmacological inhibition of COX did not affect the levels of complex I, and transduction of knockout cells with lentivirus expressing wild-type or mutant COX10 (retaining residual activity) restored complex I to normal levels. Pulse-chase experiments could not detect newly assembled complex I, suggesting that either COX is required for assembly of complex I or the latter is quickly degraded. These results suggest that in rapidly dividing cells, complex IV is required for complex I assembly or stability.