Off the beaten track: new insights into peroxisomal fission and protein sorting events in yeast

Peroxisomes are compartments in cells called organelles that perform many different functions. In humans, peroxisomal defects result in serious disorders, leading to early death. Peroxisomes need proteins to perform their function but they cannot make these proteins themselves. Therefore, peroxisomes take up (import) proteins from the cytosol, which is the fluid that surrounds organelles inside cells. Under certain conditions, peroxisome numbers need to be increased in cells, and one way to achieve this is by the division of pre-existing ones. This process is termed ‘fission’ but we do not understand fully how this occurs. In this thesis, we have studied details of the peroxisomal fission and import processes by analysing them in yeast. Pex11p is a protein which is important for peroxisome fission. Pex11p reshapes the peroxisomal membrane so that peroxisomes can start dividing. We investigated how Pex11p is stimulated to perform this function and how it interacts with the peroxisomal membrane. Our studies indicate that membrane reshaping occurs due to Pex11p interacting with specific regions of the membrane. Proteins destined for peroxisomes contain Peroxisome Targeting Signals (PTS) that are recognized by proteins Pex5p and Pex7p. These receptors transport PTS containing proteins from the cytosol, where they are made, into peroxisomes. We have identified that Aspartate aminotransferase-2 (Aat2p) localises to peroxisomes despite lacking a classical PTS. Peroxisomal localisation persisted in the absence of Pex5p and Pex7p. Instead, Pex20p is required for targeting. Functional analysis suggests that Aat2p may contribute to the regulation of metabolism inside peroxisomes