Peroxisomes are found in virtually all eukaryotic cells. They are essential organelles for many metabolic pathways in plants, fungi, and animals. The origin of peroxisomes has been hotly debated for decades. It is clear now that peroxisomes can form by fission from pre-existing peroxisomes. However, there is ample evidence for a de novo pathway of peroxisomal assembly. The endoplasmic reticulum (ER) has been implicated in this pathway, although its precise role has not been established. There have also been reports of close associations between lipid bodies (which form from the ER) and peroxisomes, although the significance of these observations is not known.
This project will test the hypothesis that lipid bodies are essential for the de novo assembly of peroxisomes in yeast. As a first step, the extent to which peroxisomal proteins reside in the lipid body-associated structures will be determined. The direct test for the hypothesis will be accomplished by looking for a precursor-product relationship between these structures and mature peroxisomes. Further confirmation will be accomplished by examining the extent of peroxisomal biogenesis in a mutant that cannot generate lipid bodies nor undergo fission of preexisting organelles.
This project thus tests a completely new model for the origin of peroxisomes. The de novo origin of peroxisomes has been a murky and controversial subject to date, and our hypothesis is consistent with several observations in the literature and could solve this controversy. If the hypothesis is correct, it would overturn current thinking of organelle biogenesis, indicating that the lipid body is capable of this activity.
The project will also provide hands-on research experience for high school (underprivileged), undergraduate, and graduate students. Results will be widely disseminated through talks at national meetings and submission to first-tier science journals.
