Diaz Francisca, Fukui Hirokazu, Garcia Sofia, Moraes Carlos T
Department of Neurology, University of Miami School of Medicine, 1095 NW 14 Terrace, Miami, FL 33136, USA.
Mol Cell Biol. 2006 Jul;26(13):4872-81. doi: 10.1128/MCB.01767-05.
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 aa3, 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.
细胞色素c氧化酶（COX）的生物合成需要COX10，它编码一种原血红素：血红素O法尼基转移酶，参与血红素a的生物合成。我们创建了COX10基因敲除小鼠细胞，这些细胞缺乏细胞色素aa3，呼吸功能缺陷，没有可检测到的复合体IV活性，并且无法组装COX。出乎意料的是，COX10基因敲除克隆中呼吸复合体I的水平显著降低。COX的药理学抑制并不影响复合体I的水平，用表达野生型或突变型COX10（保留残余活性）的慢病毒转导基因敲除细胞可使复合体I恢复到正常水平。脉冲追踪实验无法检测到新组装的复合体I，这表明要么COX是复合体I组装所必需的，要么复合体I会迅速降解。这些结果表明，在快速分裂的细胞中，复合体IV是复合体I组装或稳定性所必需的。
