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New insights into the mechanism of T-2 toxin cytotoxicity: stress granules inhibit the mTORC2/AKT signaling pathway

文献类型： 外文期刊

作者： Jiang, Tianqing 1 ; Deng, Luyu 1 ; Lin, Ruqin 1 ; Jiang, Jun 1 ; Zeng, Jian 4 ; Wen, Jikai 1 ; Deng, Yiqun 1 ;

作者机构： 1.South China Agr Univ, State Key Lab Swine & Poultry Breeding Ind, Guangzhou 510642, Guangdong, Peoples R China

2.Guangdong Acad Agr Sci, Guangzhou 510640, Guangdong, Peoples R China

3.South China Agr Univ, Coll Life Sci, Guangdong Prov Key Lab Dev Biol & Environm Adaptat, Guangzhou 510642, Guangdong, Peoples R China

4.Shaoguan Univ, Sch Biol & Agr, Guangdong Prov Key Lab Utilizat & Conservat Food &, Shaoguan 512005, Guangdong, Peoples R China

关键词： T-2 toxin; Cytotoxicity; Stress granules; mTORC2; AKT

期刊名称：FOOD BIOSCIENCE （ 影响因子：5.9； 五年影响因子：6.1 ）

ISSN： 2212-4292

年卷期： 2025 年 68 卷

页码：

收录情况： SCI

摘要： T-2 toxin is a highly poisonous mycotoxin, which contaminates crops and feed, causes poisoning of livestock and poultry, and even threatens human health through food residues. However, there is a lack of specific detoxification agents for T-2 toxin. Our previous study has shown that stress granules (SGs) most likely contribute significantly to the cytotoxicity of T-2 toxin, but the mechanism remains unclear. SGs are membraneless organelles containing proteins and untranslated mRNAs that form in response to oxidative stress, toxins, and other external stimuli. Here, we discovered for the first time that mTORC2 was able to localize to SGs. T-2 toxin recruited mTORC2 to SGs by promoting the interaction between the mTORC2 co-factor SIN1 and the core SG protein G3BP1. Upon stimulation of cells by T-2 toxin, mTORC2 was sequestered in SGs and could not activate AKT. The inhibition of the mTORC2/AKT pathway results in increased cytotoxicity of T-2 toxin, as this pathway is essential for cell survival. Furthermore, we discovered that mTORC2 probably plays a role in regulating SG assembly. Together, these findings highlight the relevance of the mTORC2/AKT pathway in the process of SGs regulating the cytotoxicity of T-2 toxin and provide new insights into the toxicological mechanism of T-2 toxin.

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