The role of peroxisomes in ageing
The role of peroxisomes in ageing
A typical feature of peroxisomes is the presence of hydrogen peroxide producing oxidases together with catalase, which decomposes hydrogen peroxide. Hydrogen peroxide is a very reactive compound, which can damage vital macromolecules such as nucleic acids, proteins and lipids. Intracellular accumulation of damaged components contributes to cellular ageing - a process that can be defined as the deterioration of cells in time, accompanied by gradual loss of cell viability.
In the Molecular Cell Biology group we study cellular ageing using yeast as simple model organisms, focusing on the role of peroxisomes (Manivannan et al., 2012).
The role of peroxisomal antioxidant enzymes in ageing.
It is generally accepted that hydrogen peroxide can contribute to ageing. Peroxisomes are cell organelles in which hydrogen peroxide can be massively produced. Using the yeast Hansenula polymorpha as a model organism, we study the role of peroxisomal anti-oxidant enzymes in ageing. Antioxidant enzymes are enzymes that degrade reactive oxygen species (ROS), such as hydrogen peroxide.
We have analyzed the role of peroxisomal catalase by comparing the lifespan of wild-type yeast cells with that of mutant cells lacking peroxisomal catalase. Unexpectedly, at conditions of relatively low hydrogen peroxide production, cells without catalase showed a longer life span than wild-type control cells. In contrast, when massive amounts of hydrogen peroxide were produced, cells lacking catalase lived shorter than wild-type controls (Kawalek et al., 2013)
Further analysis revealed that low levels of hydrogen peroxide have a positive effect on yeast viability by inducing various stress response proteins that contribute to the removal of ROS. When high amounts of hydrogen peroxide are produced cellular damage occurs, which shortens the lifespan of the cell.
At present we study the role of another peroxisomal antioxidant enzyme, the peroxiredoxin Pmp20, in yeast ageing (Bener et al., 2008)
Peroxisomal quality control and ageing
We have identified a protease which is crucial for the removal of (oxidatively) damaged peroxisomal matrix enzymes. This protease, designated Pln, belongs to the family of Lon proteases. We showed that the absence of Pln results in the accumulation of toxic peroxisomal protein aggregates and a reduction of cell viability. These observations suggest that peroxisomal protein quality control is important to prevent cellular ageing (Bener et al., 2007; Bartoszeweska et al. 2012
We recently discovered a second mechanism by which cells prevent the accumulation of protein aggregates inside peroxisomes. Once peroxisomal protein aggregates are formed, the organelle first divides, followed by degradation of the aggregate-containing organelle by autophagy (Manivannan et al., 2013).
The role of peroxisomal metabolism in yeast chronological ageing
Yeast chronological lifespan (CLS) is the time non-dividing yeast cells remain viable. We analyzed the role of peroxisomal metabolism on yeast CLS.
Studies in the yeast Hansenula polymorpha revealed that methylamine, which is metabolized by peroxisomal amine oxidase, enhances the viability of ageing cells, because it is used as extra energy source by the non-dividing cells (Kumar et al., 2012).
Using the yeast Saccharomyces cerevisiae, we analyzed the importance of intact peroxisomes in chronological ageing (Lefevre et al., 2013).
We showed that cells of peroxisome-deficient mutants have a reduced CLS compared to wild-types controls. This could be explained by the strongly decreased capacity of the peroxisome deficient cells to oxidize fatty acids, a process that in wild type cells is confined to peroxisomes. In non-dividing cells, various intracellular components are recycled, which leads to the release of fatty acids (e.g. autophagy and lipid body degradation). During chronological ageing, these fatty acids are metabolized by peroxisomal β-oxidation, thereby supplying the non-dividing cells with energy and removing the toxic free fatty acids. In peroxisome deficient cells this process is strongly disturbed causing a reduction in viability.
|Last modified:||18 May 2018 12.15 p.m.|