WITHDRAWN: Mitochondria: a critical target in the toxicity of trichothecenes and potential treatment strategies

// Deyu Huang 1 , Luqing Cui 2 , Qinghua Wu 3, 4 , Hafiz I. Hussain 2 , Menghong Dai 2 , Zainab Fatima 2 , Xu Wang 2 and Zonghui Yuan 1, 2 1 Department of Animal Sciences & Technology, Key Laboratory for the Detection of Veterinary Drug Residues, Huazhong Agricultural University, Wuhan, China 2 Department of Animal Sciences & Technology, Laboratory of Quality & Safety Risk Assessment for Livestock and Poultry Products, Huazhong Agricultural University, Wuhan, China 3 Department of Life Science, Institute of Biomedicine, Yangtze University, Jingzhou, China 4 Department of Chemistry, Faculty of Science, University of Hradec Kralove, Hradec Kralove, Czech Republic Correspondence to: Xu Wang, email: Wangxu@mail.hzau.edu.cn Zonghui Yuan, email: yuan5802@mail.hzau.edu.cn Keywords: trichothecene; mitochondria; oxidative stress; microRNA; apoptosis Received: November 13, 2017 Accepted: January 02, 2018 Epub: January 09, 2018 ABSTRACT Trichothecenes are secondary metabolites produced by fungi of genus Fusarium . It was known that trichothecenes can bind to the 60S subunit of the eukaryotic ribosomes, resulting in inhibition of protein synthesis. However, emerging evidences suggest that trichothecenes can target the mitochondria to induce mitochondrial dysfunction and mitochondria-dependent apoptosis. Numerous studies have investigated the mitochondria-associated toxicities induced by trichothecenes. Here, we mainly collected the data associated with mitochondria and its relationship with trichothecene-induced toxic effects. We showed that mitochondria are the main site of reactive oxygen species production and mediate the trichothecene-induced apoptosis in various cells. The mitochondrial membrane permeabilization plays critical roles in this apoptotic process. Trichothecenes can penetrate the mitochondrial membrane due to its amphiphilic property, and inhibit the activities of mitochondrial respiratory chain complexes and electron transfer in mitochondria. Besides, trichothecenes reduce the mitochondrial biogenesis and mitochondrial transcription and translation. Peroxisome proliferator-activated receptor-γ co-activator 1α and mammalian target of rapamycin pathway are closely linked to this process. Trichothecenes can activate various microRNAs that may mediate the protein synthesis inhibition. These microRNAs may have a crosstalk with mitochondria to mediate the mitochondrial dysfunction and transcription repression in mitochondrial genome. Numerous natural compounds have been tested for their effective antioxidant and anti-inflammatorycapacities. Specially, mitochondria-targeted antioxidants and mitophagy exhibit outstanding cytoprotective abilitysince they can reduce the mitochondrial reactive oxygen species and maintain the mitochondrial quality. This review may shed some new light on the mitochondria-associated mechanism underlying the toxicity of trichothecenes and new preventive ways to combat these mycotoxins.