Revisiting Kadenbach: Electron flux rate through cytochrome c‐oxidase determines the ATP‐inhibitory effect and subsequent production of ROS

Vogt, Sebastian; Rhiel, Annika; Weber, Petra; Ramzan, Rabia

doi:10.1002/bies.201600043

Cited by 16 publications

(16 citation statements)

References 147 publications

(178 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…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%

A thermal gradient modulates the oxidative metabolism and growth of human keratinocytes

et al. 2017

View full text Add to dashboard Cite

During their spatial and differentiative progression, keratinocytes face a thermal gradient, from 37 °C in the proliferating basal layer to 32 °C found in skin surface. In our study, we hypothesized that this difference in temperature must be balanced by increasing the heat produced during respiratory activity. We demonstrated that at 33 °C human primary keratinocytes and HaCaT cells raised mitochondrial energy metabolism, but not glycolytic activity. At 33 °C, the increased mitochondrial ATP synthesis was associated with a strong induction of the modulator of the respiratory chain estrogen receptor β, whereas uncoupling protein 1 expression was not changed. The enhanced mitochondrial oxidative metabolism was accompanied by a remarkable reduction in proliferation. These results suggest that environmental temperature can modulate the energy metabolism and proliferation of human keratinocytes.

show abstract

Section: Resultsmentioning

confidence: 99%

A thermal gradient modulates the oxidative metabolism and growth of human keratinocytes

et al. 2017

View full text Add to dashboard Cite

show abstract

“…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%

Crosstalk between Mitochondrial Fission and Oxidative Stress in Paraquat-Induced Apoptosis in Mouse Alveolar Type II Cells

Zhao

Cao

et al. 2017

Int. J. Biol. Sci.

View full text Add to dashboard Cite

Paraquat (PQ), as a highly effective and nonselective herbicide, induces cell apoptosis through generation of superoxide anions which forms reactive oxygen species (ROS). Mitochondria, as regulators for cellular redox signaling, have been proved to play an important role in PQ-induced cell apoptosis. This study aimed to evaluate whether and how mitochondrial fission interacts with oxidative stress in PQ-induced apoptosis in mouse alveolar type II (AT-II) cells. Firstly, we demonstrated that PQ promoted apoptosis and release of cytochrome-c (Cyt-c). Furthermore, we showed that PQ broke down mitochondrial network, enhanced the expression of fission-related proteins, increased Drp1 mitochondrial translocation while decreased the expression of fusion-related proteins in AT-II cells. Besides, inhibiting mitochondrial fission using mdivi-1, a selective inhibitor of Drp1, markedly attenuated PQ-induced apoptosis, release of Cyt-c and the generation of ROS. These results indicate that mitochondrial fission involves in PQ-induced apoptosis. Further study demonstrated that antioxidant ascorbic acid inhibited Drp1 mitochondrial translocation, mitochondrial fission and attenuated PQ-induced apoptosis. Overall, our findings suggest that mitochondrial fission interplays with ROS in PQ-induced apoptosis in mouse AT-II cells and mitochondrial fission could serve as a potential therapeutic target in PQ poisoning.

show abstract

“…is a rate-limiting step. Decreased expression of COX 4 results in an impaired Cytochrome c oxidase activity [ 4 , 5 ]. We hypothesize subsequent mitochondrial dysfunction associated with the formation of increased reactive oxygen species and inadequate maintenance of ATP levels when subunit 4 is reduced in the holoenzyme.…”

Section: Introductionmentioning

confidence: 99%

“…Ischemic damage and reperfusion injury of myocardium proceed with an “Overspending ATP” and finally metabolic break down. The CytOx (complex IV) is directly involved and has the “center stage” [ 4 , 5 ]. This enzyme is considered to be the rate limiting step of electron transfer chain (ETC) [ 6 , 7 ].…”

Section: Introductionmentioning

confidence: 99%

Myocardial insufficiency is related to reduced subunit 4 content of cytochrome c oxidase

Vogt

Ruppert

Pankuweit

et al. 2018

J Cardiothorac Surg

Self Cite

View full text Add to dashboard Cite

BackgroundTreatment of heart failure remains one of the most challenging task for intensive care medicine, cardiology and cardiac surgery. New options and better indicators are always required. Understanding the basic mechanisms underlying heart failure promote the development of adjusted therapy e.g. assist devices and monitoring of recovery. If cardiac failure is related to compromised cellular respiration of the heart, remains unclear. Myocardial respiration depends on Cytochrome c- Oxidase (CytOx) activity representing the rate limiting step for the mitochondrial respiratory chain. The enzymatic activity as well as mRNA expression of enzyme’s mitochondrial encoded catalytic subunit 2, nuclear encoded regulatory subunit 4 and protein contents were studied in biopsies of cardiac patients suffering from myocardial insufficiency and dilated cardiomyopathy (DCM).MethodsFifty-four patients were enrolled in the study and underwent coronary angiography. Thirty male patients (mean age: 45 +/− 15 yrs.) had a reduced ejection fraction (EF) 35 ± 12% below 45% and a left ventricular end diastolic diameter (LVEDD) of 71 ± 10 mm bigger than 56 mm. They were diagnosed as having idiopathic dilated cardiomyopathy (DCM) without coronary heart disease and NYHA-class 3 and 4. Additionally, 24 male patients (mean age: 52 +/− 11 yrs.) after exclusion of secondary cardiomyopathies, coronary artery or valve disease, served as control (EF: 68 ± 7, LVEDD: 51 ± 7 mm). Total RNA was extracted from two biopsies of each person. Real-time PCR analysis was performed with specific primers followed by a melt curve analysis. Corresponding protein expression in the tissue was studied with immune-histochemistry while enzymatic activity was evaluated by spectroscopy.ResultsGene and protein expression analysis of patients showed a significant decrease of subunit 4 (1.1 vs. 0.6, p < 0.001; 7.7 ± 3.1% vs. 2.8 ± 1.4%, p < 0.0001) but no differences in subunit 2. Correlations were found between reduced subunit 2 expression, low EF (r = 0.766, p < 0.00045) and increased LVEDD (r = 0.492, p < 0.0068). In case of DCM less subunit 4 expression and reduced shortening fraction (r = 0.524, p < 0.017) was found, but enzymatic activity was higher (0.08 ± 0.06 vs. 0.26 ± 0.08 U/mg, p < 0.001) although myocardial oxygen consumption continued to the same extent.ConclusionIn case of myocardial insufficiency and DCM, decreased expression of COX 4 results in an impaired CytOx activity. Higher enzymatic activity but equal oxygen consumption contribute to the pathophysiology of the myocardial insufficiency and appears as an indicator of oxidative stress. This kind of dysregulation should be in the focus for the development of diagnostic and therapy procedures.

show abstract

Revisiting Kadenbach: Electron flux rate through cytochrome c‐oxidase determines the ATP‐inhibitory effect and subsequent production of ROS

Cited by 16 publications

References 147 publications

A thermal gradient modulates the oxidative metabolism and growth of human keratinocytes

A thermal gradient modulates the oxidative metabolism and growth of human keratinocytes

Crosstalk between Mitochondrial Fission and Oxidative Stress in Paraquat-Induced Apoptosis in Mouse Alveolar Type II Cells

Myocardial insufficiency is related to reduced subunit 4 content of cytochrome c oxidase

Contact Info

Product

Resources

About