Cellular Ageing Deciphering the role of Peroxisomes in Yeast

Abstract

Ageing is a necessary evil experienced by all living organisms. It results in a progressive decline in the normal functioning of cells and eventually culminates with the death of the organism. Budding yeast has emerged as an appropriate model organism for ageing research and is used to study two aspects of ageing namely replicative and chronological ageing. Various studies have emphasized the function of subcellular organelles in the regulation of yeast ageing. One such organelle that is ubiquitously present in all eukaryotic cells is the peroxisome. and#946;-oxidation of fatty acids and metabolism of reactive oxygen species are the conserved functions of peroxisomes. The proliferation of this organelle is extensively studied in various model organisms. However, the molecular mechanisms that link peroxisomes with ageing are still under investigation. Our study sought to comprehend the alterations in peroxisome dynamics during replicative and chronological ageing to understand their role in yeast ageing. The changes in peroxisome number and morphology upon were first investigated in wild type (WT) cells cultured in peroxisome-inducing oleic acid (OA) and non-inducing glucose (YND) media conditions. An increase in peroxisome number was observed in early replicatively aged wild type (WT) cells in both media. However, the increase was higher in OA as compared to the YND medium. Upon chronological ageing, the cells displayed increased mean and maximal CLS in OA medium. We also observed a change in phenotype of peroxisomes from punctate to cytosolic with the progression of ageing. Interestingly, OA grown cells displayed delayed change in the phenotype. This suggests an intricate link between the morphology/protein import of peroxisomes and chronological ageing. Further to address the effect of reduced peroxisome number upon yeast ageing, we investigated pex11, pex25 and pex11pex25 cells which lack proteins involved in peroxisome fission. Among these, pex11pex25 cells had the most reduced peroxisome number. Reduction in peroxi