Loss of kinase Atg1 increases yeast maintenance energy requirement

Abstract

Maintenance of cellular homeostasis underlies healthy aging. The processes involved in homeostasis rely on the so-called maintenance energy requirement and changes in this maintenance energy requirement impact aging and survival. Among maintenance processes, autophagy plays a crucial role as it is involved in the turn-over and recycling of damaged cellular material, such as organelles or proteins. The contribution of autophagy to the maintenance energy requirement is however unknown. Taking advantage of the high degree of conservation of autophagy between humans and Saccharomyces cerevisiae, we have used this yeast as a model organism to study the impact of macroautophagy on the maintenance energy requirement. The combination of the GFP-Atg8 cleavage assay with yeast retentostat cultures showed that autophagy is highly active in chronologically aging yeast cells, in non-dividing, but non-starving conditions. Deletion of the autophagy-activating kinase ATG1, homolog of human ULK1, resulted in a 60% increase in the maintenance energy requirement and doubled the specific death rate. Both these increases cannot be solely attributed to an observed increase in loss of respiratory capacity. Intriguingly, loss of Atg1 only reduced GFP-Atg8 cleavage by 20% under these conditions, indicating that Atg1-indendent modes of autophagy might be active. Overall, we illustrate the importance of autophagy on the energetics of aging cells and propose an alternative system for the widely applied yeast stationary phase cultures in chronological aging studies.