Versicolorin A (VERA) is a mycotoxin produced by Aspergillus section Flavi species that is frequently detected in foodstuffs, particularly in corn. VERA is a precursor of aflatoxin B₁ (AFB₁), which is currently considered to be the most hazardous mycotoxin. While AFB₁ has been shown to impair oxidative phosphorylation (OXPHOS), the impact of VERA on mitochondrial function has not been extensively documented until now. The aim of the present study was to investigate the effect of VERA on mitochondrial function in intestinal Caco-2 cells. To this end, OXPHOS was assessed by measuring the oxygen consumption rate using the Seahorse™ real-time analyzer. In contrast to AFB₁, a low concentration of VERA (5 µM) was a strong uncoupler of OXPHOS and inhibited respiratory complexes I and III within a few minutes of exposure. After 24 h of exposure, VERA reduced the transcription of all mitochondrial genes encoding proteins involved in the electron transfer chain as well as decreasing the rate of OXPHOS. This effect was associated with the simultaneous down expression of two genes encoding proteins involved in the initiation phase of mitochondrial DNA transcription: POLRMT and TFB2M. Moreover, VERA induced down expression of genes coding for upstream key glycolytic enzymes, hexokinase and phosphofructokinase. These effects led to a reduced rate of ATP production associated with a cytotoxic effect. Given the significant implications of mitochondrial dysfunction for human health, it is crucial to consider the potential involvement of VERA in mitochondrial diseases.

中文翻译：

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黄曲霉毒素 B1 的前体 Versicolorin A 损害人肠道 Caco-2 细胞的线粒体功能


Versicolorin A （VERA） 是由曲霉属 Flavi 属产生的霉菌毒素，经常在食品中检测到，尤其是在玉米中。VERA 是黄曲霉毒素 B₁ （AFB₁） 的前体，目前被认为是最危险的霉菌毒素。虽然 AFB₁ 已被证明会损害氧化磷酸化 （OXPHOS），但直到现在，VERA 对线粒体功能的影响尚未得到广泛记录。本研究的目的是探讨 VERA 对肠道 Caco-2 细胞线粒体功能的影响。为此，通过使用 Seahorse™ 实时分析仪测量耗氧率来评估 OXPHOS。与 AFB₁ 相比，低浓度的 VERA （5 μM） 是 OXPHOS 的强解偶联剂，并在暴露后几分钟内抑制呼吸复合物 I 和 III。暴露 24 小时后，VERA 减少了编码电子转移链中涉及的蛋白质的所有线粒体基因的转录，并降低了 OXPHOS 的速率。这种效应与编码参与线粒体 DNA 转录起始阶段的蛋白质的两个基因同时下表达有关：POLRMT 和 TFB2M。此外，VERA 诱导编码上游关键糖酵解酶、己糖激酶和磷酸果糖激酶的基因的下表达。这些作用导致与细胞毒性作用相关的 ATP 生成速率降低。鉴于线粒体功能障碍对人类健康的重大影响，考虑 VERA 可能参与线粒体疾病至关重要。