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Enhanced SIRT1-TFEB Interaction Promotes Lysosome Biogenesis and Autophagy by Reducing TFEB Acetylation: Revealing the Enterotoxicity Disparity of Deoxynivalenol and T-2 Toxin

文献类型： 外文期刊

作者： Xu, Qiang 1 ; Lin, Ruqin 1 ; Jiang, Tianqing 1 ; Deng, Luyu 1 ; Wu, Yuting 1 ; Yuan, Qianqian 1 ; Qi, Xueying 1 ; Mu, Peiqiang 1 ; Jiang, Jun 1 ; Deng, Yiqun 1 ; Wen, Jikai 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, Guangdong Prov Key Lab Dev Biol & Environm Adaptat, Guangzhou 510642, Guangdong, Peoples R China

关键词： deoxynivalenol; T-2 toxin; autophagy; lysosome; TFEB; SIRT1; acetylation

期刊名称：JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY （ 影响因子：6.2； 五年影响因子：6.4 ）

ISSN： 0021-8561

年卷期： 2025 年 73 卷 21 期

页码：

收录情况： SCI

摘要： Multiple environmental factors contribute to digestive system damage caused by food contamination in both humans and animals. Mycotoxins, such as deoxynivalenol (DON) and T-2 toxin, have emerged as the most significant factors due to their extensive contamination and difficulty in removal. Transcription factor EB (TFEB) serves as a crucial transcriptional regulator governing lysosomal biogenesis and autophagy, a lysosomal-driven degradation system that safeguards cells against harmful stressors. However, little is known about whether the post-translational modification of TFEB affects autophagy activity, which could explain the toxicity disparity between DON and T-2 toxin. Here, we discovered that T-2 toxin induces excessive autophagy by significantly reducing TFEB acetylation, whereas DON surprisingly inhibits autophagy activity via maintaining high TFEB acetylation, which impairs lysosomal biogenesis, thereby boosting their respective toxicity. Mechanically, the T-2 toxin decreases TFEB acetylation via enhanced SIRT1-TFEB interaction and SIRT1 deacetylase activity, while DON maintains high TFEB acetylation by reversing the process. Together, our study revealed that the acetylation state of TFEB mediated by SIRT1 alters autophagy phenotypes in intestinal cells, shedding light on the various toxicological mechanisms and an important target of DON and T-2 toxin.

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