Identification of novel peroxisome functions in yeast

Abstract

Peroxisomes are ubiquitous cell organelles that play a central role in cellular lipid and hydrogen peroxide metabolism. These organelles also fulfill several non-metabolic functions related to stress and stress adaptation. Although they contribute to the generation of harmful reactive oxygen species (ROS), peroxisomes also possess enzymes to maintain redox balance and counteract oxidative stress. Peroxisomal defects in humans result in severe disorders which are often lethal, illustrating the importance of these organelles. The research described in this thesis aimed to identify novel peroxisomal functions in yeasts, which play an important role as simple model organisms in cell biology. We identified a novel peroxisomal protein with a functional peroxisome targeting signal (PTS). However, the absence of this protein did not affect yeast cells sensitivity to stress conditions. Next in our study, we demonstrated how nicotinamidase (Pnc1), which does not contain a PTS, is imported into the peroxisomes by piggybacking onto a PTS containing protein, glycerol-3-phosphate dehydrogenase (Gpd1). We showed that Pnc1 physically interacts with Gpd1 allowing its piggyback import to peroxisomes. We also identified a novel peroxisomal membrane protein, Pex37, which is required for peroxisome fission and segregation between the mother cell and the bud. Additionally, we explored the role of a vacuolar membrane protein, Vac8 and identified that it is required for ER-vacuole contact sites (NVJs) formation and vacuole inheritance. Identification of novel peroxisome functions will open doors to endless research possibilities to explore and provide a more coherent understanding of the role of peroxisomes in multiple cellular functions.