Redox Control of Copper Biotransformation and Its Toxicity Cascades in Microalgae

The redox-active nature of Cu is a key factor in its toxicity, yet the mechanisms underlying the Cu biotransformation remain poorly understood. In this study, we investigated how the cell wall interface of the freshwater microalga <i>Chlamydomonas reinhardtii</i> modulated Cu biotransformation. Our findings revealed that membrane-localized and intracellular Cu biotransformation might be closely linked to redox differentiation. Specifically, cell wall deficiency might alter the redox conditions in the cell wall-plasma membrane space, resulting in a significant accumulation of intracellularly labile Cu(I). This surge in labile Cu(I) caused oxidative stress by modifying the redox environment in cell-wall-deficient (CW) cells, leading to reactive oxygen species (ROS) generation. Concurrently, these redox changes might regulate the intracellular Cu biotransformation processes, disrupting the dynamics of the intracellular labile Cu(I)/Cu(II) cycle. In response to the oxidative stress induced by abnormal Cu biotransformation, CW cells activated the GSH system to scavenge excess ROS and stabilize internalized labile Cu(I). However, prolonged disruption of Cu biotransformation led to adverse effects, including mitochondrial fragmentation and impaired photosynthetic performance. To mitigate this cytotoxicity, CW cells deployed additional detoxification strategies, such as the assembly of lysosome-related organelles and the synthesis of polyphosphate, which sequestered excess labile Cu(I) and helped to maintain cellular homeostasis.