A surge of copper accumulation in cell division revealed its cyclical kinetics in synchronized green alga Chlamydomonas reinhardtii

Trace transition metal uptake is tightly associated with cellular biological processes. Herein, we demonstrated that copper (Cu) bioaccumulation and uptake were controlled by the cell cycle. A cyclical kinetics of Cu bioaccumulation and surge in S/M phase were observed in the synchronized green algae Chlamydomonas reinhardtii. The labile Cu(I) content also increased in the S/M phase, although the increase was moderate. Based on the comparative analysis of bioaccumulation and transcriptome data, we found the CRR1-mediated Cu uptake pathway, and CTR1 and CTR2 transporters were regulated by the intracellular Cu quota and suppressed during cell division with high Cu content. In contrast, we hypothesized a novel intracellular Cu-quota-independent Cu(I) uptake pathway in which the transporter COPT1 might be responsible for the Cu influx during cell division. Besides, a plunge of ATX1 expression level was also observed during cell division, which indicated an inhibition of the secretory pathway of Cu with the participation of ATX1 in terms of transcriptome level, probably resulting in reduced Cu efflux. Additionally, both fluorometric probe staining and transcriptomic data demonstrated that mitochondria were the dominant destination for the extra Cu content in S/M phase. Finally, some cytotoxic responses were also observed in S/M phase. Pathways related to reactive oxygen species and glutamine metabolic process were enriched in GO term and KEGG enrichment analysis, and glutathione content and cell membrane permeability determined by fluorometric probes also increased during cell division. This study showed a sharp increase of Cu uptake in cell division and revealed the genetic regulation mechanisms for the cell cycle control of Cu uptake. © 2023 Elsevier B.V.