Fluorinated liquid crystal monomers (FLCMs), emerging contaminants from electronic waste, exhibit environmental persistence and bioaccumulative potential. Despite their growing detection in humans and aquatic systems, the subcellular mechanisms of their metabolic toxicity remain poorly understood. Here, zebrafish (Danio rerio) embryos and larvae were exposed to five representative FLCMs (0.05-50 µg/L) to investigate mitochondrial and metabolic disruption. Exposure to environmentally relevant concentrations significantly reduced basal respiration by 25.0-49.8 %, ATP-linked oxygen consumption by 25.0-65.5 %, NAD⁺/NADH ratio by 32.8-84.4 %, and membrane potential by 2.5-10.8 %, indicating oxidative phosphorylation dysfunction. Concurrent upregulation of cytoplasmic isocitrate dehydrogenase (ICDHc) and α-ketoglutarate dehydrogenase (α-KGDH) activities suggested compensatory activation of the tricarboxylic acid (TCA) cycle. Targeted gene expression analysis revealed downregulation of pdk2 (-24.6 %), accompanied by increased expression of gls (+40.6 %) and mt-nd1 (+72.1 %), consistent with an AMPK-associated metabolic shift. Co-exposure with the AMPK inhibitor Compound C reversed these alterations, restoring acetyl-CoA, NAD⁺, and TCA intermediates. Targeted metabolomics and KEGG enrichment further confirmed AMPK- associated rerouting of carbon flux toward amino acid-driven anaplerosis. Overall, these findings identify FLCMs as sublethal mitochondrial toxicants and highlight the AMPK-glutamate-TCA axis as a mechanistic hallmark of metabolic disruption, raising concern that such reprogramming may increase susceptibility to metabolic disorders.
Wang et al. (2026) studied this question.