Conférence scientifique | Centre de recherche du CHU Sainte-Justine
Lysosome homeostasis, remodeling and integrity by the IntraLumenal Fragment pathway
Conférencier :
Christopher Brett, Ph.D. (pour l'axe Maladies immunitaires et cancers)
Professeur agrégé de biologie
Université Concordia, Montréal, Canada
Biographie
Dr. Christopher Brett is a cell biologist and Associate Professor of Biology at Concordia University in Montreal. His research group studies lysosome physiology primarily using baker’s yeast (Saccharomyces cerevisiae) and its vacuolar lysosome as models. Found within all eukaryotic cells, lysosomes are miniature biomaterial recycling centers important for clearing toxins, coordinating signals and supplying nutrients. These functions are critical for survival and underlie diverse physiology. As such, lysosomal dysfunction contributes to many human diseases, e.g. cancers and Alzheimer’s disease. Three fundamental processes are required for lysosome function: membrane fusion to receive biomaterials, breakdown of biomaterials into their constituents by lumenal acid hydrolases, and translocation of products (amino acids, nucleotides, lipids) across the lysosome membrane by nutrient transporter proteins so that they may be reused by the cell. Despite their importance to physiology, relatively little is known about lysosomal nutrient transporter proteins, including how their activities or lifetimes are controlled. However, Dr. Brett’s group recently discovered a new cellular pathway responsible for regulating their lifetimes that relies on generation of IntraLumenal membrane Fragments (ILFs) during lysosome membrane fusion. Termed the ILF pathway, this mechanism selectively clears transporter proteins from lysosome membranes and degrades them in response to substrates, misfolding or cell signaling. Together with a second, similar mechanism, termed the vReD pathway, his group found that the ILF pathway is critical for lysosome homeostasis, remodeling and integrity necessary for cell metabolism, proteostasis and protection against cell death. Distinct underlying mechanisms and contributions of each pathway to physiology and disease will be discussed.
