Physiological, metabolomic, and transcriptomic analyses reveal the dynamic redox homeostasis upon extended exposure of Dunaliella salina GY-H13 cells to Cd.

The study was done to elucidate the molecular mechanisms underlying the steady maintenance of the green microalga Dunaliella salina GY-H13 in successive subcultures in F/2 medium supplemented with the high cadmium (Cd) concentration (5 mg L-1) for 3 months or 84 days using physiological, metabolomic, and transcriptomic methodologies. Physiological analysis indicated that Cd suppressed growth rate, photosynthetic efficiency, and pigment contents and promoted Cd accumulation, reactive oxygen species (ROS) generation and lipid peroxidation. UPLC-MS/MS-based metabolic analysis identified the top most upregulated and downregulated metabolites, the 5'-dehydroxyadenosine and thiamine acetic acid that were associated with the formation and removal of H2O2. RNA-seq-based transcriptomic analysis showed the overrepresentation of low-CO2-inducible genes in the most downregulated gene set. Metabolomic and transcriptomic analyses further showed that the decreased GSSG/GSH-based redox potential, increased oxidative-phosphorylation gene expression, and reduced activity of TCA cycle in cells after extended exposure to Cd. Taken together, our results imply that cellular defense to Cd in D. salina is achieved by upregulation of ROS-scavenging activities including depletion of thiamine acetic acid. Dynamic redox homeostasis is maintained in cells with extended exposure to Cd by production of both oxidants and antioxidants through multiple pathways.