MERCURY · Chemical compounds targeting MERCs: identification of their partners in physiological and pathological conditions

Chemical compounds targeting MERCs: identification of their partners in physiological and pathological conditions

Mitochondria and Endoplasmic Reticulum Contact Sites (MERCs) are sites where the surfaces of these two organelles are side by side. Recently, MERCs have received considerable attention because they play an important role in several cell processes, including regulating calcium and lipid homeostasis, mitochondria fission and fusion, and apoptosis. To execute and regulate these processes, MERCs must be dynamic and respond to the needs and metabolic state of the cell. Interestingly, the organelles remain separated by a narrow cleft, typically 10-50 nm apart. The size of the gap between the organelles and its width (i.e. the area of a membrane involved in the contacts) are the critical parameters that determine their cellular functions. Although the molecular nature of MERCs has been extensively studied, the composition of their tethering structures and the underlying processes that regulate their plasticity and functionality are not fully understood. To clarify these “mysterious” contacts, the MERCURY project focused on the regulation of MERCs by small molecules. The project had two major objectives: first, to identify compounds that modulate MERCs. As a next step, selected molecules would be modified to create affinity probes. Second objective was to unravel the protein targets of the small molecules using the developed affinity probes. This would be of great relevance and importance to the field, as it is still not understood how metabolic changes “drive” MERCs to change their width and size. Since MERCs not only regulate organelle functions under physiological conditions, but may also play important roles in a number of diseases (e.g. type 2 diabetes and neurodegenerative diseases such as Alzheimer’s and Parkinson’s diseases), elucidation of the molecules that modulate their (patho)physiological functions may even be of clinical relevance (for drug repurposing or developing new drugs and using the identified molecules as the “lead compounds”). I am convinced that the MSCA fellowship and the opportunity of a postdoctoral stay at the University of Padua has had a great impact on my future career. First of all, it allowed me to change my research area and learn new methods to complement my “research portfolio”. Second, it was a great stepping stone to becoming an independent scientist. I had many chances to present and discuss my project, to see and discuss the projects of my colleagues, and to learn from others. This opportunity has also allowed me to meet and discuss with world-class scientists and to find out more about the responsibilities of a senior position and to get to know the big picture of science. Third, I have learned not only scientific skills, but also management skills (managing orders, payments, deliveries) and new soft skills (leadership techniques, communicating with other people and companies).

Текст от CORDIS, на английски · Данни: CORDIS, © Европейски съюз