Kinetic Modeling of the Mitochondrial Energy Metabolism of Neuronal Cells : The Impact of Reduced α-Ketoglutarate Dehydrogenase Activities on ATP Production and Generation of Reactive Oxygen Species

Joint Authors

Berndt, Nikolaus
Bulik, Sascha
Holzhütter, Hermann-Georg

Source

International Journal of Cell Biology

Issue

Vol. 2012, Issue 2012 (31 Dec. 2012), pp.1-11, 11 p.

Publisher

Hindawi Publishing Corporation

Publication Date

2012-06-10

Country of Publication

Egypt

No. of Pages

11

Main Subjects

Biology

Abstract EN

Reduced activity of brain α-ketoglutarate dehydrogenase complex (KGDHC) occurs in a number of neurodegenerative diseases like Parkinson's disease and Alzheimer's disease.

In order to quantify the relation between diminished KGDHC activity and the mitochondrial ATP generation, redox state, transmembrane potential, and generation of reactive oxygen species (ROS) by the respiratory chain (RC), we developed a detailed kinetic model.

Model simulations revealed a threshold-like decline of the ATP production rate at about 60% inhibition of KGDHC accompanied by a significant increase of the mitochondrial membrane potential.

By contrast, progressive inhibition of the enzyme aconitase had only little impact on these mitochondrial parameters.

As KGDHC is susceptible to ROS-dependent inactivation, we also investigated the reduction state of those sites of the RC proposed to be involved in ROS production.

The reduction state of all sites except one decreased with increasing degree of KGDHC inhibition suggesting an ROS-reducing effect of KGDHC inhibition.

Our model underpins the important role of reduced KGDHC activity in the energetic breakdown of neuronal cells during development of neurodegenerative diseases.

American Psychological Association (APA)

Berndt, Nikolaus& Bulik, Sascha& Holzhütter, Hermann-Georg. 2012. Kinetic Modeling of the Mitochondrial Energy Metabolism of Neuronal Cells : The Impact of Reduced α-Ketoglutarate Dehydrogenase Activities on ATP Production and Generation of Reactive Oxygen Species. International Journal of Cell Biology،Vol. 2012, no. 2012, pp.1-11.
https://search.emarefa.net/detail/BIM-496363

Modern Language Association (MLA)

Berndt, Nikolaus…[et al.]. Kinetic Modeling of the Mitochondrial Energy Metabolism of Neuronal Cells : The Impact of Reduced α-Ketoglutarate Dehydrogenase Activities on ATP Production and Generation of Reactive Oxygen Species. International Journal of Cell Biology No. 2012 (2012), pp.1-11.
https://search.emarefa.net/detail/BIM-496363

American Medical Association (AMA)

Berndt, Nikolaus& Bulik, Sascha& Holzhütter, Hermann-Georg. Kinetic Modeling of the Mitochondrial Energy Metabolism of Neuronal Cells : The Impact of Reduced α-Ketoglutarate Dehydrogenase Activities on ATP Production and Generation of Reactive Oxygen Species. International Journal of Cell Biology. 2012. Vol. 2012, no. 2012, pp.1-11.
https://search.emarefa.net/detail/BIM-496363

Data Type

Journal Articles

Language

English

Notes

Includes bibliographical references

Record ID

BIM-496363