Save the mitochondria
Scientists from Pushchino are looking for new mitochondrial protection factors
Tatiana Perevyazova, ITEB RAS press service.
How to protect brain and heart cells from death during a serious circulatory disorder? Scientists from the Institute of Theoretical and Experimental Biophysics of the Russian Academy of Sciences in Pushchino (ITEB RAS) intend to answer this question, whose project "Elucidation of the molecular nature of the external mitochondrial nucleotide-binding regulator of the nonspecific Ca2+-dependent pore (mitochondrial permeability transition pore, mPTP) and its role in the protection of mitochondria and cells in pathological conditions" was supported by the Russian scientific foundation.
If an organ has stopped being supplied with blood, then its tissues begin to gradually die. In medicine, this disease is called ischemia. Due to the lack of nutrition contained in the blood, the cells die massively. And this process of cell death starts in the mitochondria.
Mitochondria are one of the key parts of the cell where their fuel and energy potential are produced. If the mitochondria suffer from a lack of nutrition, pores open in their outer membrane membranes, through which the cells receive a signal to die.
The nonspecific mitochondrial pore (mPTP) – as scientists call it – has been studied for more than 40 years. The pioneer in this field was the American scientist John J. Lemasters (J.J. Lemasters). Three years ago, he founded the Laboratory of pharmacological regulation of cell resistance at the ITEB RAS under the megagrant of the Ministry of Education and Science, bringing together leading mitochondrial scientists and young promising researchers.
Despite the long history of study, the molecular nature of the mitochondrial pore remains largely unclear. Scientific groups around the world are looking for ways to force the pores of mitochondria to close, so as not to encourage cells to mass death in diseases. So far, only one drug, cyclosporine A, used for ischemia or reperfusion, has proven its effectiveness. Several other drugs that inhibit mPTP are undergoing clinical trials. So this area is open for research.
The authors of the ITEB RAS project focused on the search for substances that regulate the opening or closing of the mitochondrial pore. A few years ago, they proved that some nucleotides in the cytosol of a cell under certain conditions affect mPTP. But scientists suspect that there is a hitherto unknown nucleotide regulating the pore in the outer membrane or intermembrane space of the mitochondria. That's what they want to find and study. The results of proteomic studies conducted within the framework of the megagrant will help them in this. Scientists have already selected proteins that can indicate an unknown nucleotide. They will create models on cells and isolated mitochondria of various animals and humans. Then, by selecting the parameters of the mitochondrial pores, the desired factor will be calculated.
"If we find targets whose binding of cytosolic nucleotides leads to the suppression of mPTP, then this will make it possible to begin the development of penetrating highly effective analogues that can be used to treat the consequences of ischemic disease," Anna Nikiforova, project manager, researcher, Candidate of Biological Sciences, explained to the press service of ITEB RAS.
The project is designed for two years. The RNF has allocated three million rubles for it.
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