Sedanur YILMAZ, Hızlan Hıncal AĞUŞ, Cansın Ogeday ŞENGÖZ

Crosstalk between autophagy and apoptosis induced by camphor in Schizosaccharomyces pombe

Camphor is widely used in pharmacy, the food industry, and cosmetics. In this study, we evaluate inhibitory and cytotoxiceffects of camphor in the fission yeast (Schizosaccharomyces pombe), which presents a unicellular model in mechanistic toxicology andcell biology. Low-dose camphor exposure (0.4 mg/mL) activated autophagy, which was shown by GFP-Atg8 dots and transcriptionalupregulation of Atg6 (Beclin-1 ortholog). Autophagy was also confirmed by using autophagy-deficient cells, which showed reduction inGFP-Atg8 dot formation. However, high-dose camphor exposure (0.8 mg/mL) caused dramatic cell death ratios, demonstrated by spotand colony-forming assays, even in autophagy-deficient cells. To unravel the underlying mechanism, this time, apoptosis-deficient cellswere exposed to low- and high-dose camphor. Apoptosis was also confirmed by acridine orange/ethidium bromide staining. Amongyeast apoptosis mediators, Aif1 was found to mediate camphor-induced cell death. In conclusion, differential regulation of autophagyand apoptosis, and switches between them, were found to be dose-dependent. The potential effects of camphor on autophagy andapoptotic cell death and underlying mechanisms were clarified in basic unicellular eukaryotic model, S. pombe.

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