Use of thiacalix[4]arene C-1193 for a directed influence on the functional activity of mitochondria and simulation of this process using a Petri nets

• Published in: Biotechnologia (Poznan) 2024, Vol.105 (1), p.69-81
• Main Authors: Danylovych, Hanna, Danylovych, Yurii, Chunikhin, Alexander, Cherenok, Sergiy, Kalchenko, Vitaly, Kosterin, Sergiy
• Format: Article
• Language: English
• Subjects: calcium; mitochondria; petri nets; reactive nitrogen and oxygen species; Research Papers; thiacalixarenes
• ISSN: 0860-7796; 2353-9461
• DOI: 10.5114/bta.2024.135643

In molecular biological studies, considerable attention is paid to macrocyclic nanoscale compounds known as calix[4]arenes. An imperative concern in biochemical membranology and molecular biotechnology is the exploration of effectors capable of modifying the intensity of redox reactions within the inner mitochondrial membrane and influencing the activity of its Ca transport systems. The simulation model development is relevant to formalize and generalize the experimental data and assess the conformity of experimental results with theoretical predictions. Experiments were carried out on a suspension of isolated rat myometrial mitochondria. The synthesized thiacalix[4]arene C-1193, containing four sulfur atoms, was employed. Demonstrations of time-dependent and concentration-dependent (0.01-10 μM) inhibition of Ca accumulation and reactive oxygen species (ROS) formation by mitochondria in the presence of C-1193 were observed. While C-1193 inhibited the oxidation of NADH and FADH , it did not induce mitochondrial swelling. The thiacalix[4]arene also inhibited the synthesis of nitric oxide, with a Ki of 5.5 ± 1.7 nM, positioning it as a high-affinity blocker of endogenous NO generation in mitochondria. These results are the basis for the possible application of the synthesized thiacalix[4]arene as a tool in researching biochemical processes in mitochondria. A simulation model employing functional hybrid Petri nets was developed, reproducing the functional activity of mitochondria, including simultaneous NADH oxidation, ROS formation, NO synthesis, and Ca accumulation. The derived equations formalize and describe the time dependencies of the listed processes in the medium under the influence of thiacalix[4]arene C-1193.