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Our mission is to understand the molecular underpinnings of fundamental lysosome and exosome biology
and to translate state-of-the-art knowledge into strategies that enhance longevity and treat disease.
Lysosomes are the recycling compartments of eukaryotic cells, the basic units of life. First discovered by Dr. Christian De Duve (pictured here), these tiny "stomachs" of cells are important sources of nutrients and are needed to clear toxic biomaterials. Cells become more dependent on these functions, and lysosomes, as they age. Lysosomes are also important for programmed cell death. Thus, lysosome biology plays a major role in longevity.
3 Basic Processes ARE Needed for
• Membrane fusion, to receive incoming biomaterials to be recycled
• Biomaterial catabolism, by lumenal acid hydrolases that breakdown proteins, complex carbohydrates and fats into their constituents
• Nutrient transport, by polytopic proteins embedded in the lysosome membrane that return amino acids, sugars and lipids to the cell for reuse
In the Brett Lab, we study two of these fundamental processes: lysosome membrane fusion and nutrient transport.
We are particularly interested in how these processes change in response to cellular aging. This research has led us to discover, among other things, a mechanism responsible for lysosome membrane and nutrient transporter turnover called the ILF pathway.
McNally et al. (2017) Dev. Cell
Here we describe the IntraLumenal Fragment (ILF) pathway, an unconventional (ESCRT-indepednent) polytopic protein degradation pathway responsible for lysosome protein quality control and organelle membrane remodeling.
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