Abstract
Cytochrome c oxidase (CytOx), the oxygen-accepting and rate-limiting enzyme of mitochondrial respiration, binds with 10 molecules of ADP, 7 of which are exchanged by ATP at high ATP/ADP-ratios. These bound ATP and ADP can be exchanged by cholate, which is generally used for the purification of CytOx. Many crystal structures of isolated CytOx were performed with the enzyme isolated from mitochondria using sodium cholate as a detergent. Cholate, however, dimerizes the enzyme isolated in non-ionic detergents and induces a structural change as evident from a spectral change. Consequently, it turns off the “allosteric ATP-inhibition of CytOx”, which is reversibly switched on under relaxed conditions via cAMP-dependent phosphorylation and keeps the membrane potential and ROS formation in mitochondria at low levels. This cholate effect gives an insight into the structural-functional relationship of the enzyme with respect to ATP inhibition and its role in mitochondrial respiration and energy production.
Highlights
In mitochondria cytochrome c oxidase (CytOx) represents the rate limiting step of the respiratory or electron transmission chain (ETC)
We have shown that reversible dimerization of CytOx regulates mitochondrial respiration mediated by Calcium and cAMP
Binding of cholate to the enzyme during the isolation procedure results in a dimeric cholate the enzyme during the isolation results in ausing dimeric form Binding of CytOxof[12]
Summary
In mitochondria cytochrome c oxidase (CytOx) represents the rate limiting step of the respiratory or electron transmission chain (ETC). We have shown that reversible dimerization of CytOx regulates mitochondrial respiration mediated by Calcium and cAMP. This mechanism has recently been shown in intact isolated rat heart mitochondria [3] describing how mitochondrial respiration is controlled by the ATP/ADP-ratio via the “allosteric ATP-inhibition” [4]. This mechanism guarantees optimal ATP synthesis, moderate oxygen uptake and low generation of reactive oxygen species (ROS) [5] and is stated as the “second mechanism of respiratory control” [6]
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