Proteins Prohibitins Can Become New Targets for Drugs From Obesity

Newswise — Scientists from Immanuel Kant Baltic Federal University analyzed scientific works dedicated to the role of proteins prohibitins in the development of obesity. It turned out that these proteins promote development of inflammation both in separate cells and the whole organism. This happens because prohibitins stimulate emission of anti-inflammatory substances by immune cells, and also participate in destruction of mitochondria damaged during oxidative stress. Obtained information points to the fact that prohibitins can become targets for medicine aimed at struggle with obesity consequences. Results of the research are published in the magazine Frontiers in Molecular Biosciences.

According to WHO statistic in 2022 43% of all adult Earth population had overweight, by this 16 % of people had obesity. Overweight makes many organ systems suffer: cardiovascular, respiratory, locomotive ones. Moreover, obesity leads to molecular changes in cells. Thus, for example, in that case genes activating ageing and cell death, and also inflammatory reactions are triggered. Inflammation in its turn leads to oxidative stress, destroys cell metabolism and work of mitochondria – “energetic stations” of a cell.

Researches show that prohibitins play the important role in maintaining stability of many intracellular processes – division, work of mitochondria, activation of genes and other. However the information about their participation in inflammatory response during obesity was so far fragmentary, that didn’t allow to treat them as potential therapeutic target for struggle with negative consequences of overweight.

Scientists from Immanuel Kant Baltic Federal University (Kaloningrad) together with colleagues from Siberian State Medical University (Tomsk) analyzed scientific articles that described location, levels and function of prohibitins during development of obsession. It turned out that these proteins normally occur on membranes of various immune cells – lymphocytes, macrophages, mast cells. They correlate with receptors – molecules in the membrane, that perceive external signals – and stimulate release of anti-inflammatory substances. Inflammation usually occurs in tissues as a result of injury or appearance of infection and helps the organism to get rid of dangerous substances and pathogens. In the case of obesity, it appears in response to satiation of fat tissue’s cells with lipids.

Scientists also found prohibitins on membranes of mitochondria. Here proteins control quality of mitochondrial DNA and answer for destruction of mitochondria damaged due to oxidative stress. By this in the case of destruction of DNA prohibitins participate in delivery of short “cut” fragments of these molecules from mitochondria to cytoplasm, that leads to development of inflammatory reaction. On the other hand, prohibitins don’t let “healthy” mitochondria to divide uncontrolled and blend, so preventing decline of their integrity and work.

There is another location of prohibitins in cells – nucleus. Abnormal accumulation of these proteins in the nucleus turned out to be closely connected with distortion of cell division and cell-cycle block.

Besides this, authors of the review found in texts of scientific works tests of drugs that had prohibitins as their target. Thus, scientists found out low-molecular (small in mass and size) substances, that while changing the activity of these proteins, force the destruction of fat tissue’s cells, activate the use of glucose accumulated in them and so prevent weight gain. Besides this some research groups reported about anti-inflammatory and antitumoral action of small molecules, that interact with prohibitins, for example, flavoglins and bacterial capsular polysaccharide Vi.

“Our analysis has shown that prohibitins can be treated as a potential molecular target for drugs from obesity. However, tissue-specific action of these proteins and different variants of their localization – in membranes, mitochondria, nucleus – demands further and more careful examination. It enables to understand the role of prohibitins in development of metabolic syndrome and obesity in more detail. In future we are planning to continue theoretic and practical (laboratory) work in this direction and more thoroughly examine the role of prohibitins (together with other proteins) in cells of peripheral blood, adipocytes and hepatocytes of human in a normal condition and during pathology, making stress on signaling pathways and function of mitochondria on in vitro conditions”, – tells Natalia Todosenko, candidate of biological sciences, senior associate of Center of Immunology and Cell Biotechnology, Immanuel Kant Baltic Federal University.