Peroxisome homeostasis and ageing in yeast

Studies on the molecular mechanisms involved in ageing are facilitated by using simple model organisms including yeast. In this thesis we focussed on the chronological lifespan of yeast, which is defined as the time a cell can survive in a non-dividing state. The studies revealed that acidification of the growth medium as well as resistance of the cells to low pH are major determinants in yeast chronological lifespan. This implies that medium pH should be carefully controlled when analysing the effects of gene mutations on yeast ageing.
Ageing of a cell is characterized by a progressing increase in damage to cellular constitutes hampering their biological functions. Reactive oxygen species (ROS) are a major cause of damage. In eukaryotic cells these compounds are predominantly produced in mitochondria and peroxisomes. Within peroxisomes ROS are detoxified by the antioxidant enzymes catalase and the peroxiredoxin Pmp20. Interestingly, our data indicate that cells that lack these antioxidant enzymes can have an extended lifespan. The absence of catalase was associated with compensatory upregulation of ROS detoxifying enzymes outside peroxisomes. These observations indicate that ROS produced within peroxisomes may act outside the organelle. The research in this thesis also supports the emerging view that exposure of cells to low doses of ROS may be beneficial for the cells.