Grant: Operating Grant

Peroxisomes are one kind of intracellular membrane-enclosed compartments called organelles. Peroxisomes perform a number of different important biochemical functions, most notably in fat metabolism and the detoxification of reactive oxygen species like hydrogen peroxide. The necessity of peroxisomes for normal human development and physiology is underscored by the lethality of the human peroxisome biogenesis disorders, genetic diseases in which peroxisomes fail to be assembled correctly in the cell. As the pathway that leads to the formation of peroxisomes has been highly conserved during evolution, we exploit yeast as a model system to investigate the molecular mechanisms underlying the peroxisome biogenesis disorders. Of the thirteen genes which when mutated give rise to the peroxisome biogenesis disorders, twelve were first identified in yeast. Therefore, yeast is a valid and valuable system with which to investigate the molecular bases of the peroxisome biogenesis disorders. Our research aims for a comprehensive molecular understanding of how peroxisomes are made in the cell and how this assembly pathway goes awry in cells of peroxisome biogenesis disorder patients, with the ultimate goal of developing a rational therapeutic intervention for treating these patients.