Curcumin delays cytokinesis in fission yeast by targeting the septin ring

Curcumin is the active compound of one of the most widely used spices in the world. It has also been highly valued as a traditional health supplement in many South Asian countries for millennia. More recently, this plant extracted small molecule has attracted strong attention for its therapeutic potential. Nevertheless, the molecular and cellular targets of curcumin remain unknown. Here, we undertook a novel imaging-based approach to determine the intracellular distribution of curcumin using the model organism fission yeast Schizosaccharomyces pombe by taking advantage of the intrinsic fluorescence of curcumin. Live fluorescence microscopy revealed for the first time that curcumin, at a concentration of just one micromolar, formed a narrow circumferential ring around the equatorial plane of dividing cells within minutes after being added to the yeast culture. The intensity of this ring increased proportionally to the concentration of curcumin and gradually over time. The curcumin ring co-localized both spatially and temporally with septin ring and the exocyst complex at the equatorial plane during cytokinesis. Deletion of one of the septin genes spn4 reduced the frequency of curcumin ring by 74%. Micromolar concentrations of curcumin slowed down the contractile ring constriction by up to 49% in a dosage dependent manner. Besides fission yeast, curcumin similarly targets the division plane of two other yeasts, Saccharomyces cerevisiae and Candida albicans. Thus, curcumin, originated from plants, targets the septin cytoskeleton to delay yeast cytokinesis, suggesting its potential as both an antifungal therapeutic option and a fluorescence probe for yeast septins.