Burke P V, Poyton R O
Department of Molecular, Cellular, and Developmental Biology, University of Colorado, Boulder, CO 80309-0347, USA.
J Exp Biol. 1998 Apr;201(Pt 8):1163-75. doi: 10.1242/jeb.201.8.1163.
Eukaryotic cytochrome c oxidases are complex oligomeric membrane proteins composed of subunit polypeptides encoded by both nuclear and mitochondrial genomes. While the mitochondrially encoded subunits are encoded by unique genes, some of the nuclear-encoded subunits are encoded by multigene families. The isoforms produced by these multigene families are tissue-specific and/or developmentally regulated in mammals and environmentally regulated in lower eukaryotes. Isoforms for one of the subunits, V, in the yeast Saccharomyces cerevisiae and one of the subunits, VII, in the slime mold Dictyostelium discoideum are regulated differentially by oxygen concentration. Extensive studies with the yeast subunit V isoforms have revealed that the genes for these proteins are switched on or off at very low oxygen concentrations (0.5-1 micromol l-1 O2) and that they affect the catalytic properties of holocytochrome c oxidase differentially. By altering an internal step in electron transfer between heme a and the binuclear reaction center (composed of heme a3 and CuB), the 'hypoxic' isoform, Vb, enhances the catalytic constant three- to fourfold relative to the 'aerobic' isoform, Va. Modeling studies suggest that this occurs by an interaction between transmembrane helix VII of subunit I and the transmembrane helix in subunit V. The inverse regulation of these two isoforms allows cells to assemble different types of holoenzyme isoenzymes in response to oxygen concentration. Oxygen also regulates the level of transcription of the genes for the other nuclear-coded subunits of yeast cytochrome c oxidase and affects the level of two of the mitochondrially encoded subunits (I and II) post-transcriptionally. Thus, the level of cytochrome c oxidase activity that is produced at different oxygen tensions in yeast is determined in part by the number of holoenzyme molecules that are assembled and in part by the oxygen-regulated isoforms of subunit V. The possibility that this type of control exists in other organisms is considered.
真核细胞细胞色素c氧化酶是由核基因组和线粒体基因组编码的亚基多肽组成的复杂寡聚膜蛋白。线粒体编码的亚基由独特的基因编码，而一些核编码的亚基则由多基因家族编码。这些多基因家族产生的同工型在哺乳动物中是组织特异性的和/或发育调控的，在低等真核生物中是环境调控的。酿酒酵母中的一个亚基V和盘基网柄菌中的一个亚基VII的同工型受氧浓度的差异调节。对酵母亚基V同工型的广泛研究表明，这些蛋白质的基因在极低的氧浓度（0.5-1微摩尔/升O2）下开启或关闭，并且它们对全细胞色素c氧化酶的催化特性有不同的影响。通过改变血红素a和双核反应中心（由血红素a3和CuB组成）之间电子传递的内部步骤，“低氧”同工型Vb相对于“有氧”同工型Va将催化常数提高了三到四倍。模型研究表明，这是通过亚基I的跨膜螺旋VII与亚基V中的跨膜螺旋之间的相互作用发生的。这两种同工型的反向调节使细胞能够根据氧浓度组装不同类型的全酶同工酶。氧还调节酵母细胞色素c氧化酶其他核编码亚基基因的转录水平，并在转录后影响两个线粒体编码亚基（I和II）的水平。因此，酵母在不同氧张力下产生的细胞色素c氧化酶活性水平部分取决于组装的全酶分子数量，部分取决于亚基V的氧调节同工型。人们考虑了这种控制类型存在于其他生物体中的可能性。
