2016
DOI: 10.1002/bies.201600043
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Revisiting Kadenbach: Electron flux rate through cytochrome c‐oxidase determines the ATP‐inhibitory effect and subsequent production of ROS

Abstract: Mitochondrial respiration is the predominant source of ATP. Excessive rates of electron transport cause a higher production of harmful reactive oxygen species (ROS). There are two regulatory mechanisms known. The first, according to Mitchel, is dependent on the mitochondrial membrane potential that drives ATP synthase for ATP production, and the second, the Kadenbach mechanism, is focussed on the binding of ATP to Cytochrome c Oxidase (CytOx) at high ATP/ADP ratios, which results in an allosteric conformationa… Show more

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Cited by 16 publications
(11 citation statements)
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“…When ATP is not consumed, the ATP/ADP ratio rises and respiration slows to state 4. Moreover, the studies by Kadenbach and colleagues have proposed that ATP exerts a negative allosteric modulation of the activity of complex IV . For all these reasons, a lower expenditure of ATP should not increase the amount of mitochondrial ATP.…”
Section: Resultsmentioning
confidence: 99%
“…When ATP is not consumed, the ATP/ADP ratio rises and respiration slows to state 4. Moreover, the studies by Kadenbach and colleagues have proposed that ATP exerts a negative allosteric modulation of the activity of complex IV . For all these reasons, a lower expenditure of ATP should not increase the amount of mitochondrial ATP.…”
Section: Resultsmentioning
confidence: 99%
“…It has been reported that increased generation of ROS requires dynamic change of mitochondrial fission 38 , and Drp1 play a major role in regulating ROS production in apoptosis 39 . Previous studies showed that the induction of the peroxidase activity of Cyt-c is a key event in early apoptosis 40 , while the production of ROS, one of the primary factor of oxidative stress, is determined by Cyt-c-oxidase 41 . In this study, during AT-II cells of PQ intoxication, we detected the ROS production and release of Cyt-c and found that suppression of Drp1 by Mdivi-1 can block ROS generation and Cyt-c release.…”
Section: Discussionmentioning
confidence: 99%
“…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 ]. Although different mechanisms regulate the function of CytOx [ 7 , 8 ], the inhibition of CytOx by ATP occurring at very high ATP/ADP ratios [ 9 ] is allosterically controlled by the dimeric conformation [ 3 ]. However, to work with the isolated enzyme requires the enzymatic preparation with cholate [ 10 , 11 ] that actually induces a stable dimerization of CytOx itself [ 12 ].…”
Section: Introductionmentioning
confidence: 99%