Electronic mitochondrion of mammalian cells

The last decades was marked by great number of achievement in the understanding of life basis. The new volume of knowledge led to principally new approaches both in the biology and in the different biomedical supplements. Progress touched on not only diagnostic methods but also notions about course of diseases and therapy directly. The appropriate evolutional transition from curing of organism and organs to the cellular (as well as sub-cellular and genetic) therapy takes place.

A lot of severe diseases (atherosclerosis, cardiomyopathy, ischemic disease, valvular lesions, congestive heart failures and many others) are known to be caused by action of active forms of oxygen (AFO). There are facts that AFO take part in the process of cells and organisms ageing. It was shown before that the reason of AFO appearance is incomplete reduction of molecular oxygen in the mitochondrion (sub-cellular structures, main ATP sources). It is side reaction during the oxidative phosphorylation, and its intensity depends on regime of mitochondrion functioning: amount of oxygen, respiratory substrates and adenylates. AFO have very high chemical activity and provoke appearance the number of reactions which finally lead to damages of membranes, proteins, DNA and irreversible mutations. First of all, mitochondrion suffers from AFO.

The cell has multilayer protection for struggle with oxidative stress (antioxidant system), when take part some enzymes and cofactors, in particular, superoxide dismutase, catalase, tocopherol (vitamin E), ascorbic acid (vitamin C). In many cases, for example, during prolong anoxaemia, antioxidant system is unable to cope with large quantity of radicals, that can lead to irreversible damages and even cell death. Some researchers suppose that damages of cells and mitochondria by action of oxidative stress provoke increase of AFO generation.

At the present time oxidative phosphorylation and antioxidant system of mitochondrion (the key pathways for oxidative stress understanding) have been studied well. Individual constituents of these processes were investigated but that is not the case for connections and interactions between them, when the entire picture still absences.

In order to reveal the situation with the active forms of oxygen in the cell, the systems approach is needed, which considers all the metabolites and enzymes as a whole system, in contrast to reductive one, making conclusions on the basis of results for every separate part of system. Practical instrument for realization of approach for solution of concrete task of metabolic pathway description can be mathematic model created by means of kinetic modeling. Such method allows creating not only qualitative but also quantitative models. The task solution in full allows not only reply the questions answered but also give recommendations for solution of AFO problem.

Prepared model allow describing both normal conditions in the cell and various extreme states and regimen, for example, oxidative stress, deficiency of substrates etc. During the model calculation we can monitor any metabolites concentrations, any rates and fluxes, that is difficult and sometimes impossibly during the experiment. The ability to monitor all the mitochondrion parameters, modeling the real conditions in the cell, allows proposing new methods of therapy and possibly evening new types of drugs.

 

Download

Select language

RussianEnglish

Contacts

Institute for Systems Biology SPb

Moscow, Leninskie Gory, 1, build.75G, office. 613, Science park, 119992

+7(495)930-8407,   +7(495)930-8407, +7(495)783-8718

insysbio@insysbio.ru   insysbio@insysbio.ru

Search