PhD ceremony Ms. S. Manivannan: Yeast peroxisomes. De novo formation and maintenance

PhD ceremony: Ms. S. Manivannan

Dissertation: Yeast peroxisomes. De novo formation and maintenance

Promotor(s): prof. I.J. van der Klei

Faculty: Mathematics and Natural Sciences

Peroxisomes are important eukaryotic organelles, consisting of a protein rich matrix, surrounded by a single membrane. Generalized functions include β-oxidation of fatty acids and detoxification of hydrogen peroxide.

Currently, it is highly debated how peroxisomes are formed. In wild-type yeast cells the organelles primarily develop by fission of pre-existing ones. However, it has been proposed that they can also form de novo from the endoplasmic reticulum (ER) in mutant cells fully lacking peroxisomal membrane structures (e.g. pex3 or pex19), upon reintroduction of the corresponding genes. Studies described in this thesis revealed, however, in these mutants, pre-peroxisomal structures are present, which serve as template for re-introduction of peroxisomes. Hence, under these conditions peroxisomes do not derive from the ER.

Peroxisome homeostasis involves a delicate balance between peroxisome biogenesis and degradation (pexophagy). We demonstrate that the presence of protein aggregates in the peroxisomal matrix had physiological disadvantages as it affected growth of the cells and caused enhanced levels of reactive oxygen species. These protein aggregates promoted asymmetric peroxisome fission and degradation of peroxisomes containing protein aggregates via autophagy

Finally, this thesis describes a novel function for the peroxisomal membrane protein Wsc, which is important for peroxisome fission and segregation in glucose-grown yeast cells.