Hartig

Eukaryotic cells contain intracellular membrane-surrounded compartments (organelles) to separate metabolic pathways. This spatial separation ensures optimal flux of metabolic intermediates and increases the efficiency of the metabolism. Peroxisomes are highly versatile organelles and essential for life. They participate in many metabolic processes, most notably the degradation of fatty acids and the glyoxylate cycle. Synthesis of organelles and their degradation has to be

Eukaryotic cells contain intracellular membrane-surrounded compartments (organelles) to separate metabolic pathways. This spatial separation ensures optimal flux of metabolic intermediates and increases the efficiency of the metabolism. Peroxisomes are highly versatile organelles and essential for life. They participate in many metabolic processes, most notably the degradation of fatty acids and the glyoxylate cycle. Synthesis of organelles and their degradation has to be tightly regulated in agreement with the metabolic status of the cell. Accordingly, peroxisomes need to be maintained in sufficient number to ensure metabolic homeostasis. A network of interacting proteins guarantees the biogenesis of functional peroxisomes, the transport of peroxisomal matrix proteins across the organellar membrane, and the control of size, shape and number of these compartments. Dispensable peroxisomes are degraded in a process called pexophagy. Employing yeast as model system we aim to elucidate the molecular mechanisms leading to new peroxisomes either through proliferation of already existing ones or via a de novo biogenesis pathway through fission from the ER.

Currently, our main interest is focused on the mechanism of the de novo biogenesis initiated at the ER. Proteins exclusively involved in the biogenesis of peroxisomes are called peroxins (Pex-proteins). Among these the Pex11 protein is a membrane elongation factor, and in yeast, we showed that this protein acts only on already existing peroxisomes leading to proliferation. Two distantly related yeast proteins, Pex25p and Pex27p, play similar roles at the peroxisomal membrane and, in addition, participate in the de novo biogenesis. The Pex3 protein is the only peroxin demonstrated to accumulate under certain conditions at the ER and later be transferred to peroxisomes. Distinct vesicles emanating from the ER may slowly mature into peroxisomes or may fuse with each other or already existing peroxisomes to form mature organelles. The priming event at the ER, the proteins involved and the molecular mechanism are so far unknown, and will be the focus of our future work.