Abstract

Our laboratory has previously used a high-throughput screening of commercial compound libraries to discover several natural chemicals that delay chronological aging of the baker’s yeast Saccharomyces cerevisiae. One of these chemicals is a lithocholic bile acid. We have previously shown that lithocholic acid delays yeast chronological aging by crossing the plasma membrane, accumulating in both mitochondrial membranes and remodeling lipid metabolism in mitochondria. The resulting changes in the mitochondrial membrane lipidome alter mitochondrial functionality and convert mitochondria into a signaling compartment. This signaling compartment modulates a distinct set of transcriptional factors that respond by eliciting specific changes in the transcription of many nuclear genes. The resulting changes in the cellular proteome create an aging-delaying cellular pattern because they affect many cellular processes, including an age-related death of quiescent and non-quiescent cell populations. All these aging-delaying changes that take place in yeast exposed to lithocholic acid suggest that this bile acid promotes a complex cascade of events affecting many other cellular processes. Regulated changes in reversible protein phosphorylation have been implicated in the control of many cellular processes. I sought to make a first step towards understanding how the regulated protein phosphorylation may delay yeast chronological aging in response to lithocholic acid treatment. To attain this objective, in studies described here, I used mass spectrometry-assisted proteomics to investigate possible changes in protein phosphorylation patterns within purified populations of quiescent and non-quiescent yeast cells treated with lithocholic acid. My findings indicate that lithocholic acid elicits specific changes in the protein phosphorylation pattern of quiescent and non-quiescent yeast cells.