Drug Discovery Targeting Mitochondrial Pores and Channels for Cancer, Heart and Liver Diseases
Institute of Theoretical and Experimental Biophysics of RAS, and Medical University of South Carolina
Release of proapoptotic proteins (cyt c, AIF, EndoG, SMAC etc) from mitochondria across permeabilized mitochondrial membranes plays a crucial role in the initiation of apoptosis. However, the molecular mechanism(s) underlying stress-mediated alterations in the permeability of mitochondrial membranes remains poor understood. Elucidation of these mechanisms is not only of scientific importance, but also of great practical interest for medicine. The government of the Russian Federation is supporting grant project 14.Z50.31.0028 entitled “Drug discovery targeting mitochondrial pores and channels for cancer liver and heart deceases” at the Institute of Theoretical and Experimental Biophysics of the RAS. This project is investigating the role of voltage dependent anionic channels (VDAC) and its various molecular partners (Bax, Bak, tBid hexokinase, TSPO, tubulin, vimentin) localized in the mitochondrial outer membrane in modulating outer membrane permeability and cell resistance against stress factors . Another direction of the project addresses the roles of the mitochondrial ATP-sensitive potassium channel and electrogenic Ca2+,Fe2+ uniporter in the pathogenesis of cell injury after hypoxia/reperfusion, oxidative stress and other clinically relevant damaging conditions. A major outcome of the project will be creation in the Russian Federation of a modern drug discovery laboratory for identifying of drugable small molecules targeting mitochondria pores and channels.