Abstract
Enniatins (ENNs) A1 and B1, previously considered ionophores, are emerging mycotoxins with effects on Ca(2+) homeostasis. However, their exact mechanism of action remains unclear. This study investigated how these toxins affect Ca(2+) flux in SH-SY5Y cells. ENN A1 induced Ca(2+) 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 Ca(2+) channel, as shown when nickel, which directly blocks the Ca(2+) channel pore, is added. Mitochondrial function also influenced the effects of ENN B1, as treatment with FCCP reduced toxin-induced Ca(2+) 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 Ca(2+) ionophores and suggests a different mechanism of action for each toxin.