1224 / 2024-09-20 17:30:57

BDE-47 induces apoptosis and ferroptosis in Pseudosciaena crocea kidney (PCK) cells by disrupting mitochondrial energy metabolism

Pseudosciaena crocea kidney (PCK),Apoptosis,Ferroptosis,Mitochondrial energy metabolism,2,2',4,4'-tetrabromodiphenyl ether (BDE-47)

Session 51 - The changing coastal environment: from Land-sourced pollution to marine ecological risk

2,2′,4,4′-Tetrabromodiphenyl ether (BDE-47), an emerging contaminant (EC), is widely used in the production of brominated flame retardants and is biotoxic to marine organisms. However, our understanding of the mechanism of PBDE-induced toxicity remains incomplete. In this study, BDE-47 cytotoxicity after short-term exposure was investigated in PCK cells. BDE-47 significantly decreased cell viability, and morphological alterations were observed. Moreover, BDE-47 exposure induced apoptosis and ferroptosis, a newly described form of iron-mediated cell death, as demonstrated by transcriptomic analysis and physiological/biochemical tests. The observed cell death was associated with mitochondrial damage and a decrease in ATP production. Pharmacological intervention of cytotoxicity via AICAR, an activator of the AMPK protein, a regulator of energy, strongly confirmed the causal relationship between cell death and energy metabolism dysfunction. Furthermore, lipidomic analysis revealed lipid metabolism disorders resulting from the accumulation of triglycerides (TGs) and glycerophospholipids (GPs) and the suppression of β-oxidation, ultimately inhibiting ATP synthesis. Molecular docking analysis revealed the binding potential of BDE-47 with energy metabolism checkpoints (AMPK and CPT1). Thus, our study broadens the understanding of the toxicity of BDE-47 and provides a new potential cellular and molecular mechanism.