Peroxisome biogenesis and maintenance in yeast

Peroxisomes are ubiquitous organelles in which eukaryotic cells compartmentalize a wide variety of metabolic processes. Among others, peroxisomes are involved in the metabolism of lipids and reactive oxygen species. The importance of peroxisomes for human health is highlighted by severe disorders caused by defects in peroxisome formation. The aim of this thesis was to better understand the de novo peroxisome formation pathway, which has been a subject of fervent debate during the last two decades.

We identified peroxisomal vesicles in a yeast mutant assumed to lack any peroxisomal membrane structure as a result of the absence Pex3, a key protein involved in membrane formation. Since these vesicles contain a subset of peroxisomal membrane proteins, a Pex3-independent pathway must exist. In a high-throughput fluorescence microscopy-based study, aiming to identify proteins involved in de novo peroxisome formation, we found several candidate proteins. Nevertheless, we failed to identify genes responsible for de novo peroxisome biogenesis. Finally, we show that in cells that have defects in fission and inheritance of peroxisomes, these organelles form de novo. However, this is a relatively slow process that probably does not occur in normal wild type yeast cells.