Enniatins (ENNs) A1 and B1, previously considered ionophores, are emerging mycotoxins with effects on Ca²⁺ homeostasis. However, their exact mechanism of action remains unclear. This study investigated how these toxins affect Ca²⁺ flux in SH-SY5Y cells. ENN A1 induced Ca²⁺ influx through store-operated channels (SOC). The mitochondrial uncoupler FCCP reduced this influx, suggesting that the mitochondrial status influences the toxin effect. Conversely, ENN B1 did not affect SOC but acted on another Ca²⁺ channel, as shown when nickel, which directly blocks the Ca²⁺ channel pore, is added. Mitochondrial function also influenced the effects of ENN B1, as treatment with FCCP reduced toxin-induced Ca²⁺ depletion and uptake. In addition, both ENNs altered mitochondrial function by producing the opening of the mitochondrial permeability transition pore. This study describes for the first time that ENN A1 and B1 are not Ca²⁺ ionophores and suggests a different mechanism of action for each toxin.

中文翻译：

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Enniatins A1 和 B1 通过线粒体以外的替代途径调节钙通量


恩尼亚汀 (ENN) A1 和 B1 以前被认为是离子载体，是新兴的霉菌毒素，会影响 Ca ²⁺稳态。然而，它们的确切作用机制仍不清楚。本研究调查了这些毒素如何影响 SH-SY5Y 细胞中的 Ca ²⁺通量。 ENN A1 通过存储操纵通道 (SOC) 诱导 Ca ²⁺流入。线粒体解偶联剂 FCCP 减少了这种流入，表明线粒体状态影响毒素效应。相反，ENN B1 不影响 SOC，而是作用于另一个 Ca ²⁺通道，如添加直接堵塞 Ca ²⁺通道孔的镍时所示。线粒体功能也影响 ENN B1 的效果，因为 FCCP 治疗减少了毒素诱导的 Ca ²⁺消耗和吸收。此外，两种 ENN 都通过打开线粒体通透性转换孔来改变线粒体功能。这项研究首次描述了 ENN A1 和 B1 不是 Ca ²⁺离子载体，并提出了每种毒素的不同作用机制。