scholarly journals Multiple Mechanisms Regulate Eukaryotic Cytochrome C Oxidase

Cells ◽  
2021 ◽  
Vol 10 (3) ◽  
pp. 514
Author(s):  
Rabia Ramzan ◽  
Bernhard Kadenbach ◽  
Sebastian Vogt
Keyword(s):  
Cytochrome C ◽  
Cytochrome C Oxidase ◽  
Mitochondrial Respiration ◽  
Rat Heart ◽  
Isolated Rat Heart ◽  
Atp Inhibition ◽  
Rat Heart Mitochondria ◽  
Rate Limiting ◽  
Regulatory Properties ◽  
Isolated Rat

Cytochrome c oxidase (COX), the rate-limiting enzyme of mitochondrial respiration, is regulated by various mechanisms. Its regulation by ATP (adenosine triphosphate) appears of particular importance, since it evolved early during evolution and is still found in cyanobacteria, but not in other bacteria. Therefore the “allosteric ATP inhibition of COX” is described here in more detail. Most regulatory properties of COX are related to “supernumerary” subunits, which are largely absent in bacterial COX. The “allosteric ATP inhibition of COX” was also recently described in intact isolated rat heart mitochondria.

Mitochondrial cytochrome c oxidase is inhibited by ATP only at very high ATP/ADP ratios

2017 ◽  
Vol 398 (7) ◽  
pp. 737-750 ◽  
Author(s):  
Rabia Ramzan ◽  
Andreas K. Schaper ◽  
Petra Weber ◽  
Annika Rhiel ◽  
Muhammad Saad Siddiq ◽  
...  
Keyword(s):  
Cytochrome C ◽  
Cytochrome C Oxidase ◽  
Rat Heart ◽  
Isolated Rat Heart ◽  
Heart Mitochondria ◽  
Tween 20 ◽  
Activity Measurements ◽  
Atp Inhibition ◽  
Rat Heart Mitochondria ◽  
Very High

Abstract In the past, divergent results have been reported based on different methods and conditions used for enzymatic activity measurements of cytochrome c oxidase (CytOx). Here, we analyze in detail and show comparable and reproducible polarographic activity measurements of ATP-dependent inhibition of CytOx kinetics in intact and non-intact rat heart mitochondria and mitoplasts. We found that this mechanism is always present in isolated rat heart mitochondria and mitoplasts; however, it is measurable only at high ATP/ADP ratios using optimal protein concentrations. In the kinetics assay, measurement of this mechanism is independent of presence or absence of Tween-20 and the composition of measuring buffer. Furthermore, the effect of atractyloside on intact rat heart mitochondria confirms that (i) ATP inhibition occurs under uncoupled conditions [in the presence of carbonly cyanide m-chlorophenyl hydrazone (CCCP)] when the classical respiratory control is absent and (ii) high ATP/ADP ratios in the matrix as well as in the cytosolic space are required for full ATP inhibition of CytOx. Additionally, ATP inhibition measured in intact mitochondria extends in the presence of oligomycin, thus indicating further that the problem to measure the inhibitory effect of ATP on CytOx is apparently due to the lack of very high ATP/ADP ratios in isolated mitochondria.

scholarly journals Cholate Disrupts Regulatory Functions of Cytochrome c Oxidase

Cells ◽  
2021 ◽  
Vol 10 (7) ◽  
pp. 1579
Author(s):  
Rabia Ramzan ◽  
Jörg Napiwotzki ◽  
Petra Weber ◽  
Bernhard Kadenbach ◽  
Sebastian Vogt
Keyword(s):  
Cytochrome C ◽  
Cytochrome C Oxidase ◽  
Mitochondrial Respiration ◽  
Sodium Cholate ◽  
Atp Inhibition ◽  
Ros Formation ◽  
Low Levels ◽  
Regulatory Functions ◽  
Relationship Of ◽  
Rate Limiting

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.

scholarly journals Mesalazine Induces Oxidative Stress and Cytochrome c Release in Isolated Rat Heart Mitochondria: An Analysis of Cardiotoxic Effects

2020 ◽  
Vol 39 (3) ◽  
pp. 241-247
Author(s):  
Ahmad Salimi ◽  
Farnaz Bahreini ◽  
Zhaleh Jamali ◽  
Jalal Pourahmad
Keyword(s):  
Cytochrome C ◽  
Rat Heart ◽  
Isolated Rat Heart ◽  
Mitochondrial Swelling ◽  
Heart Mitochondria ◽  
Cytochrome C Release ◽  
Mitochondrial Ros ◽  
Ros Formation ◽  
Rat Heart Mitochondria ◽  
Inflammatory Bowel

Mesalazine is widely used in the management of inflammatory bowel disease. Previous studies reported that mesalazine-induced cardiotoxicity is a rare, potentially fatal complication. Mitochondria play an important role in myocardial tissue homeostasis. Deterioration in mitochondrial function will eventually lead to cardiomyocyte death and consequently cardiovascular dysfunction. The aim of the current study was to investigate the effects of mesalazine on rat heart mitochondria. Rat heart mitochondria were isolated by mechanical lysis and differential centrifugation. Parameters of mitochondrial toxicity including succinate dehydrogenase (SDH) activity, reactive oxygen species (ROS) formation, mitochondrial membrane potential (MMP) collapse, mitochondrial swelling, and cytochrome c release were evaluated. Results revealed that mesalazine induced a concentration- and time-dependent rise in mitochondrial ROS formation, inhibition of SDH, MMP collapse, mitochondrial swelling, and cytochrome c release in rat heart mitochondria. These results indicate that the cardiotoxic effects of mesalazine are most likely associated with mitochondrial dysfunction and ROS formation, which finally ends in cytochrome c release signaling and induction of apoptosis.

Effects of pinacidil and calcium on isolated rat heart mitochondria

2012 ◽  
Vol 443 (1) ◽  
pp. 113-117 ◽  
Author(s):  
S. M. Korotkov ◽  
L. V. Emel’yanova ◽  
I. V. Brailovskaya ◽  
V. P. Nesterov
Keyword(s):  
Rat Heart ◽  
Isolated Rat Heart ◽  
Heart Mitochondria ◽  
Rat Heart Mitochondria ◽  
Isolated Rat
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