Peroxisomes are single membrane bound organelles with conserved functions in β-oxidation of fatty acids and detoxification of hydrogen peroxide. Biogenesis of peroxisomes depends on peroxins, which are encoded by PEX genes. The Saccharomyces cerevisiae Pex23 family members occur in a protein complex together with the ER reticulon proteins at ER-peroxisome contact sites, called EPCONs. The EPCONs regulate de novo peroxisome formation from the ER by controlling preperoxisomal vesicle (PPV) biogenesis. In my thesis I describe studies on all four H. polymorpha Pex23 family proteins, namely Pex23, Pex24, Pex29 and Pex32. Based on protein localization and morphological studies, I propose that all four proteins are functioning in membrane contact sites with the ER. Pex32 and Pex24 function more specifically at EPCONs and are crucial for peroxisome biogenesis, most likely for membrane lipid transport from the ER to peroxisomes. Pex23 and (overproduced) Pex24 also accumulate at nucleus vacuole junctions (NVJs). The reason for this and the function of these proteins at NVJs is still unknown. Pex29 is not essential for peroxisome biogenesis, however, deletion of PEX29 leads to fewer lipid droplets (LDs) and altered mitochondrial morphology. Possibly, Pex29 is not a genuine peroxin. Similarly, the absence of Pex23 affects LDs and mitochondria, but in addition results in abnormal peroxisome formation.
|Qualification||Doctor of Philosophy|
|Place of Publication||[Groningen]|
|Publication status||Published - 2021|