Cell cycle-dependent Cu uptake explained the heterogenous responses of Chlamydomonas to Cu exposure

Growing evidence suggested that microorganisms exhibited heterogeneous sensitivity to toxicants, but their underlying mechanisms remain largely unknown. The asynchronous cell cycle progression in natural population implies the connection between cell cycle and heterogeneity. Here, the heterogenous responses of Chlamydomonas reinhardtii upon Cu stress were confirmed with the aid of a fluorometric probe for imaging Cu(I), implying the connection with cell cycle. Our results further indicated that the increase of labile Cu(I) was related to the cell division, leading to the fluctuation of labile Cu(I) with diurnal cycle and cell cycle, respectively. However, lack of Cu mainly influenced the cell division. We demonstrated that G2/M phase was the critical stage requiring high Cu quota during cell division. Specifically, algae at G2/M phase required 10-fold of Cu quota compared with that at G1 phase, which was related to the mitochondrial replication. Eventually, the heterogeneous Cu uptake ability of algae at different cell phases led to the heterogeneous responses to Cu exposure. Overall, Cu could influence the cell cycle through mediating the cell division, and in turn algae at different cell phases exhibited different Cu sensitivities. This study firstly uncovered the underlying mechanisms of heterogeneous Cu sensitivity for phytoplankton, which could help to evaluate the potential ecological risks of Cu.