Involvement of Pca1 in ROS-mediated apoptotic cell death induced by alpha-thujone in the fssion yeast

• Published in: FEMS yeast research Vol. 20; no. 4; pp. 1 - 9
• Main Authors: Agus, Hizlan Hincal, Kok, Gizem, Derinoz, Ezgi, Oncel, Didem, Yilmaz, Sedanur
• Format: Journal Article
• Language: English
• Published: Oxford University Press 01.06.2020
• Subjects: Acetic acid; Analysis; Apoptosis; Biochemistry; Cells; Investigations; Organic acids; Superoxide
• ISSN: 1567-1356; 1567-1364
• DOI: 10.1093/femsyr/foaa022

Alpha-thujone, widely used in beverages (1-5 mg/kg), is known to have cytotoxic effects, but the mode of action and the role of potential apoptotic proteins in yeast cell death should be unraveled. In this study, we used Schizosaccharomyces pombe, which is a promising unicellular model organism in mechanistic toxicology and cell biology, to investigate the involvement of pro-apoptotic factors in alpha-thujone-induced cell death. We showed alpha-thujone-induced ROS accumulation-dependent cytotoxicity and apoptosis. In addition, we used superoxide dismutase-defcient cells (sod1 and sod2 mutants) to understand the effect of oxidative stress. Alpha-thujone caused signifcant cytotoxicity and apoptotic cell death, particularly in sod mutants. Moreover, two potential apoptotic factors, pca1 and pnu1 (pombe caspase-1 and pombe nuc1) were investigated to understand which factor mediates alpha-thujone-induced cell death. Pca1-defcient cells showed increased survival rates and reduced apoptosis in comparison to parental cells after chemical treatment while pnu1 mutation did not cause any signifcant change and the response was found identical as of parental cells. Yeast responded to alpha-thujone in caspase-dependent manner which was very similar to that for acetic acid. In conclusion, alfa-thujone-induced apoptosis and accounting mechanisms, which were mediated by ROS and driven by Pca1, were clarifed in the unicellular model, S. pombe.