Kasuya, J., Kruth, K., Lee, D., Kim, J.S., Williams, A., Kitamoto, T. (2025). Effects of lithium on mortality and metabolite profiles in Drosophila lithium-inducible SLC6 transporter mutants. Environ. Toxicol. Pharmacol. 116(): 104684.
FlyBase ID
FBrf0262552
Publication Type
Research paper
Abstract
Lithium has long been the primary treatment for bipolar disorder and shows promise for managing other neurological and psychiatric conditions. We previously identified the Lithium-inducible SLC6 transporter (List) in Drosophila melanogaster as a gene significantly upregulated in response to lithium chloride supplementation. List encodes a putative amino acid transporter belonging to the Na[+]-dependent solute carrier family 6. Here, we show that List is expressed in the Malpighian tubules, glia, and hindgut. RNA interference-mediated List knockdown in the Malpighian tubules drastically increases lithium-induced mortality. Additionally, List loss-of-function mutants (List[TG4.2]) accumulate six times more internal lithium than controls after lithium exposure. Metabolomic analysis revealed disrupted amino acid metabolism and a shift toward a more oxidized cellular redox state in lithium-treated List[TG4.2] mutants. Overall, our findings suggest that List protects flies from lithium toxicity by regulating internal lithium levels and maintaining metabolic and redox balance.
