Bar Ilan University
Engineered Novel Protein-Protein Interaction Regulators to Study Mitochondrial Function and Modulate Mitochondrial Homeostasis
SESSION 3: NOVEL MODULATORS OF BIOLOGY
Sunday, June 25, 2023, at 02:40 pm - 03:05 pm
Mitochondria are maternally inherited, cytoplasmic organelles that play central roles in maintaining cellular metabolic homeostasis, cell survival, and cell death. They are also the so-called "powerhouses" of cells as they are primarily responsible for providing the supply of adenosine triphosphate, ATP, the energy "currency" of the cell by converting oxygen and nutrients into ATP via oxidative phosphorylation in the inner mitochondrial membrane. The major mechanisms by which mitochondria maintain their homeostasis are mitochondrial quality control mechanisms such as mitophagy and mitochondrial dynamics including both fission and fusion.
Protein-protein interactions, PPIs, are central to most biological processes and are often dysregulated in many diseases, making them important therapeutic targets. Compared with the highly conserved nature of binding pockets, for example, substrate in enzyme, PPI interfaces are inherently more diverse. Hence, they offer the potential of differentiating between many proteins and even between homologous enzymes, since the sequence and/or structure of their PPI sites are usually unique. Peptides and peptidomimetics, modified peptide, are ideal candidates to target PPIs, as they demonstrate many advantages, such as conformational flexibility, high selectivity and potency.
Using a rational design approach, we developed modulators of selective PPI sites that target mitochondrial homeostasis in a highly specific and effective manner. These modulators modulate individual proteins and pivotal signaling pathways of the mitochondrial quality control mechanisms and reveal undiscovered pathways in mitochondrial homeostasis and may result in novel therapeutics that are of great clinical importance.
Protein-protein interactions represent a significant proportion of functionally relevant biological interactions, and therefore manipulating these interactions is an important therapeutic strategy. The main focus of the Qvit lab is the identification of molecular modulators of protein-protein interaction using bioinformatics analysis, peptide and protein chemistry, and system-wide biological assays. Our goal is the development of compounds capable of modulating protein complexes that will allow a better understanding of the role of specific protein-protein interactions in cells and will be a starting point for the development of therapeutic compounds.