Journal article
Effects of Lithium on Mortality and Metabolite Profiles in Drosophila Lithium-Inducible SLC6 Transporter Mutants
Environmental toxicology and pharmacology, Vol.116, 104684
06/2025
DOI: 10.1016/j.etap.2025.104684
PMCID: PMC12129673
PMID: 40194719
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 (ListTG4.2) 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 ListTG4.2 mutants. Overall, our findings suggest that List protects flies from lithium toxicity by regulating internal lithium levels and maintaining metabolic and redox balance.
•Lithium remains a key treatment for bipolar disorder.•The mechanisms behind lithium’s beneficial and adverse effects are unclear.•The Drosophila SLC6 transporter List may function as a proline transporter.•List knockdown in the Malpighian tubules increases lithium-induced mortality.•List dysfunction alters amino acid metabolism and redox signaling pathways.
Details
- Title: Subtitle
- Effects of Lithium on Mortality and Metabolite Profiles in Drosophila Lithium-Inducible SLC6 Transporter Mutants
- Creators
- Junko Kasuya - Department of Anesthesia 1-316 Bowen Science Building, 51 Newton Road, Iowa City, IA 52242, USAKarina Kruth - University of IowaDongkeun Lee - University of Iowa, Occupational and Environmental HealthJong Sung Kim - University of IowaAislinn Williams - University of IowaToshihiro Kitamoto - Department of Anesthesia 1-316 Bowen Science Building, 51 Newton Road, Iowa City, IA 52242, USA
- Resource Type
- Journal article
- Publication Details
- Environmental toxicology and pharmacology, Vol.116, 104684
- DOI
- 10.1016/j.etap.2025.104684
- PMID
- 40194719
- PMCID
- PMC12129673
- NLM abbreviation
- Environ Toxicol Pharmacol
- ISSN
- 1382-6689
- eISSN
- 1872-7077
- Publisher
- Elsevier B.V; AMSTERDAM
- Grant note
- National Institutes of Health (NIH): MH078271, MH085081, MH125838, MH111578 U.S. Department of Defense: AR220030 Brain & Behavior Research Foundation: 30056 (KK)
This work was supported by grants from the National Institutes of Health (NIH) [MH078271 and MH085081 (TK) ; MH125838 and MH111578 (AW) ] , the U.S. Department of Defense [AR220030 (AW) ] , and the Brain & Behavior Research Foundation [NARSAD Grant #30056 (KK) ] .
- Language
- English
- Electronic publication date
- 04/05/2025
- Date published
- 06/2025
- Academic Unit
- Psychiatry; Occupational and Environmental Health; The University of Iowa Institute for Vision Research; Iowa Neuroscience Institute; Anesthesia; Neuroscience and Pharmacology
- Record Identifier
- 9984808538602771
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