Protein and lipid transport in health and disease: molecular mechanisms of endocytic sorting

Lysosomal storage diseases involve an inherited enzyme deficiency caused by genetic defects. Every cell has hundreds of lysosomes, which contain digestive enzymes used to break down complex cell components such as proteins into simpler components for the cell to reuse. In lysosomal storage diseases fatty substances called sphingolipids accumulate inside brain cells and cause progressive neurological degeneration and early death. Potentially, a lack of digestive enzymes may be the root cause. Recent research also suggests that the way the brain transports cholesterol may contribute to the damage associated with these diseases. The Saccharomyces cerevisiae yeast uses genes that are similar to those found in humans to control the transport of proteins and fats inside the cell. Dr. Elizabeth Conibear is identifying these genes in yeast and in mammalian cells. The research could help reveal ways to change the transport and storage of cholesterol and other lipids, which could lead to methods of preventing accumulation of fatty substances in the brains of children with these diseases. Developing a better understanding of how the cell transports cholesterol could also have important implications for treating adults with heart disease.