Mitochondrial dynamics imbalance and energy dyshomeostasis mediated developmental toxicity of ochratoxin a in zebrafish (Danio rerio)

文献类型： 外文期刊

第一作者： Li, Meng

作者： Li, Meng;He, Mengai;Liao, Zhenfeng;Li, Chenxi;Mi, Yingqiu;Pan, Ningning;Xie, Xinyi;Liu, Zhiyu;Hou, Jiayin;Chen, Liezhong;He, Mengai;Mi, Yingqiu;Yu, Xueli

作者机构：

关键词： Ochratoxin A; Mitochondrial dynamics; Energy metabolism; Developmental toxicity; Zebrafish

期刊名称：FOOD AND CHEMICAL TOXICOLOGY （ 影响因子：3.5； 五年影响因子：4.1 ）

ISSN： 0278-6915

年卷期： 2025 年 204 卷

页码：

收录情况： SCI

摘要： Ochratoxin A (OTA) has been increasingly detected in foodstuffs and human samples. However, the molecular mechanisms of developmental toxicity induced by OTA remain poorly explored. Our results demonstrated that oxidative stress induced by OTA caused mitochondrial dysfunction in larvae, characterized by malformed mitochondria, and decreased mitochondrial membrane potential and complex II, IV and V activities. Central carbon metabolism analysis indicated that exposure to OTA induced energy metabolism disturbance by decreasing ATP contents and altering energy-relevant metabolite contents. Energy metabolism disturbance was further confirmed by transcriptomics analysis, with differentially expressed genes significantly enriching in glycolysis and TCA cycle. Additionally, molecular docking simulations and surface plasmon resonance analysis demonstrated that OTA interacted with mfn1 and mfn2, verifying its interference effects on mitochondrial dynamics. The insufficient energy supply induced by OTA activated AMP-activated protein kinase signal pathways, which accelerated catabolic processes, accompanied by decreases in yolk sac size and yolk lipid. Finally, insufficient energy supply caused developmental retardation of zebrafish larvae. Collectively, this study systematically elucidated the roles of mitochondrial dynamics imbalance and energy dyshomeostasis in the developmental toxicity induced by OTA, providing critical insights for refining food safety standards and therapeutic interventions.

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