Expression and function of cytochrome c oxidase subunit isologues. Modulators of cellular energy production?
Expression and function of cytochrome c oxidase subunit isologues. Modulators of cellular energy production?
复制标题
细胞色素c氧化酶亚基同系物的表达和功能。
DOI：
10.1111/j.1749-6632.1988.tb35344.x
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发表时间：
1988
影响因子：
5.2
通讯作者：
Farrell,LE
中科院分区：
文献类型：
--
作者：
Poyton,RO;Trueblood,CE;Wright,RM;Farrell,LE
了解非光合作用真核细胞中细胞能量产生的调节的尝试集中于线粒体呼吸链的组成部分及其三个能量守恒位点。尽管许多因素可能相互作用，影响线粒体呼吸和氧化磷酸化的速率，但最近的研究提出细胞色素c氧化酶是真核生物细胞能量产生整体调节的关键酶。”这一假设得到了许多研究结果的支持。首先，线粒体呼吸链中NADH和细胞色素c之间的氧化还原反应（即包括前两个氧化磷酸化位点的反应）接近平衡3-”，而由细胞色素c氧化酶催化的细胞色素c和0之间的氧化还原反应基本上是不可逆的。”其次，氧化磷酸化控制的应用表明，细胞色素c氧化酶是具有显着“控制强度”的两个主要步骤之一存在于高等真核生物（例如大鼠肝脏f4）和低等真核生物（例如酿酒酵母”）的线粒体中。第三，相对于某些生物体（例如，近平滑假丝酵母、5'.cerevisiaeI6）和组织（例如牛肝”）中的其他呼吸链成分，细胞色素 aa 的含量可能受到限制。第四，ATP（和其他阴离子）通过与被认为不携带细胞氧化还原中心的亚基结合，对来自多种真核生物的细胞色素 c 氧化酶的动力学特性具有显着影响。” 22 这些发现共同表明，细胞色素 c 氧化酶催化的一个或多个反应相当于代谢途径中的关键步骤，因此，它是一个重要的控制点，以某种方式将呼吸和氧化磷酸化水平与细胞能量需求相匹配。目前，尚不清楚真核细胞如何改变其细胞色素 c 氧化酶活性水平以响应能量需求的变化。这两种类型的调节通过响应时间和蛋白质合成和/或周转的要求来区分。短期调节是立即的，可能受到变构调节（通过 ATP 和/或其他代谢物z3）的影响，并且不需要蛋白质合成或周转的数量。
Attempts to understand the regulation of cellular energy production in nonphotosynthetic eukaryotic cells have focused on the components of the mitochondrial respiratory chain and its three sites of energy conservation. Although a number of factors could interact to affect the rate of mitochondrial respiration and oxidative phosphorylation, recent studies have led to the proposal that cytochrome c oxidase is a key enzyme in the overall regulation of cellular energy production in eukaryotes.’.’This hypothesis is supported by a number of findings. First, the redox reactions between NADH and cytochrome c in the mitochondrial respiratory chain (ie, those that include the first two sites of oxidative phosphorylation) are near equilibrium3-” whereas the redox reactions between cytochrome c and 0,, which are catalyzed by cytochrome c oxidase, are essentially irreversible.’Second, the application of control to oxidative phosphorylation has revealed that cytochrome c oxidase is one of two major steps that have significant “control strength” in mitochondria from both higher eukaryotes (eg rat liverf4) and lower eukaryotes (eg Saccharomyces cerevisiae”). Third, cytochromes aa, can be limiting in amount with respect to other respiratory chain components in some organisms (eg, Candida parapsilosis, 5 ‘. cerevisiaeI6) and tissues (eg bovine liver”). Fourth, ATP (and other anions) has a marked effect on the kinetic properties of cytochrome c oxidase from a variety of eukaryotes”-” by binding to subunits that are thought not to carry the redox centers of the holoenzyme. 22 Together these findings suggest that one, or more, of the reactions catalyzed by cytochrome c oxidase is equivalent to the committed step in a metabolic pathway. As such, it is an important control point that somehow matches the level of respiration and oxidative phosphorylation to cellular energy requirements. At present, it is unclear how eukaryotic cells alter their cytochrome c oxidase activity levels in response to changes in energy demand. In principle, two general types of regulation are possible: short term and long term. These two types of regulation are distinguishable by response time and by a requirement for protein synthesis and/or turnover. Short-term regulation is immediate, could be affected by allosteric regulation (via ATP and/or other metabolitesz3), and does not require protein synthesis or turnover. Long-term regulation would be affected by changing the number of