Zooming in on the localization of peroxisomal membrane proteins

All eukaryotic cells contain organelles. These are distinct cellular compartments, each fulfilling a specific function, which are surrounded by a membrane. Peroxisomes are crucial organelles containing enzymes that can break down fatty acids and toxic substances such as hydrogen peroxide. Peroxisomes vary in size and number depending on the growth conditions. Absence or malfunctioning can lead to severe disorders.

Yeasts are ideal model organisms for studying peroxisome formation and function. The size and number of peroxisomes in yeast cells are dependent on the nutrient source they are cultivated on. One of the key peroxisomal proteins is Pex3, which plays a role in peroxisome formation, the maintenance of organelles in yeast mother cells, and peroxisome degradation. Pex3 is a membrane protein that can bind different other proteins (interaction partners), making it important for various processes. However, not much is known about the interactions yet.

The research described in this thesis therefore focuses on Pex3 and its interaction partners, utilizing super-resolution microscopy. Using this technique, the location of the proteins, whether or not an interaction partner is bound, and the changes in this over time can be studied. We discovered that the interaction partners have partially overlapping binding sites on the Pex3 protein, which can lead to competition for binding Pex3. Increased protein production (overexpression) of one of the interaction partners affects the processes Pex3 plays a part in. Here, the level of overexpression is decisive. The clarified Pex3 3D structure and predictions of the interactions with the binding partners confirmed the partially overlapping binding sites, which explains the competition.