Arsenite methyltransferase 3 is required for mitochondrial function and hepatic lipid metabolism
Delaney P, Griffin J, Khan N, Ibrash B, O'Connor MJ, Venit T, Ambrosio EM, Pergantis SA, Ober E, Percipalle P, Sadler KC (2026)
Publication Type: Journal article
Publication year: 2026
Journal
DOI: 10.1111/febs.70559
Abstract
Arsenic poisoning has severe health effects, and accordingly, most research on the arsenite methyltransferase 3 (AS3MT) enzyme has focused on its role in arsenic metabolism, overlooking potential endogenous functions. We discovered an arsenic-independent role for AS3MT in regulating hepatic energy metabolism. as3mt loss in zebrafish caused differential expression of thousands of genes in the liver, with many of the downregulated genes playing roles in mitochondrial energy metabolism. Similar genes were downregulated in AS3MT-depleted human cells. as3mt zebrafish mutants had large, malformed mitochondria, were more sensitive to both arsenic and the mitochondrial toxin rotenone, and impaired swimming velocity. as3mt mutants developed steatosis, a hallmark of mitochondrial dysfunction. Restoring As3mt in hepatocytes of as3mt mutants rescued steatosis and mitochondrial gene expression. Overexpression of As3mt in wild-type hepatocytes protected against steatosis caused by iAs induced. This demonstrates a novel, conserved, endogenous role for As3mt in hepatic energy metabolism, identifies As3mt loss as a previously unrecognized cause of steatosis, and suggests that arsenic may induce mitochondrial dysfunction due to sequestering As3mt from its endogenous role.
Involved external institutions
New York University Abu Dhabi (NYU Abu Dhabi)
United Arab Emirates (AE)
Novo Nordisk Foundation / Novo Nordisk Fonden (NNF)
Denmark (DK)
University of Crete / Πανεπιστήμιο Κρήτης
Greece (GR)
United Arab Emirates (AE)
Novo Nordisk Foundation / Novo Nordisk Fonden (NNF)
Denmark (DK)
University of Crete / Πανεπιστήμιο Κρήτης
Greece (GR)
How to cite
APA:
Delaney, P., Griffin, J., Khan, N., Ibrash, B., O'Connor, M.J., Venit, T.,... Sadler, K.C. (2026). Arsenite methyltransferase 3 is required for mitochondrial function and hepatic lipid metabolism. Febs Journal. https://doi.org/10.1111/febs.70559
MLA:
Delaney, Patrice, et al. "Arsenite methyltransferase 3 is required for mitochondrial function and hepatic lipid metabolism." Febs Journal (2026).
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