Gene-Regulated Release of Distinctive Volatile Organic Compounds from Stressed Living Cells

Breath-borne volatile organic compounds (VOCs) have been increasingly studied as non-invasive biomarkers in both medical diagnosis and environmental health research. Recently, changes in breath-borne VOC fingerprints were demonstrated in rats and humans following pollutant exposures. In this study, the eukaryotic model Saccharomyces cerevisiae was used to study the release of cellular VOCs resulting from toxicant exposures (i.e., O₃, H₂O₂, and CO₂) and its underlying biological mechanism. Our results showed that different toxicant exposures caused the release of distinctive VOC profiles of yeast cells. The levels of ethyl acetate and ethyl n-propionate were altered in response to all the toxicants used in this study and could thus be targeted for future environmental toxicity monitoring. The RNA-seq results revealed significant changes in the metabolic or signaling pathways related to the ribosome, carbohydrate, and amino acid metabolisms after exposures. Notably, the shift from glycolysis to the pentose phosphate pathway of carbohydrate metabolism and the inhabitation of the aspartate pathway in the lysine synthesis was essential to the cellular antioxidation by providing reduced nicotinamide adenine dinucleotide phosphate (NADPH). The reprogrammed metabolisms could have resulted in the observed changes of VOCs released, e.g., the production of ethyl acetate for detoxification from yeast cells. This study provides further evidence that VOCs released from living organisms could be used to monitor and guard against toxic exposures while providing better mechanistic insights of the changes in breath-borne VOCs previously observed in rats and humans exposed to air toxicants.