Mechanism of deoxynivalenol mediated gastrointestinal toxicity: Insights from mitochondrial dysfunction

Abstract

Deoxynivalenol (DON) is a mycotoxin predominantly produced by Fusarium genus, and widely contaminates cereals and associated products all over the world. The intestinal toxicity of DON is well established. However, intestinal homeostasis involves mitochondria, which has rarely been considered in the context of DON exposure. We summarize the recent knowledge on mitochondria as a key player in maintaining intestinal homeostasis based on their functions in cellular energy metabolism, redox homeostasis, apoptosis, intestinal immune responses, and orchestrated bidirectional cross-talk with gut microbe. In addition, we discuss the pivotal roles of mitochondrial dysfunction in the intestinal toxicity of DON and highlight promising mitochondrial-targeted therapeutics for DON-induced intestinal injury. Recent studies support that the intestinal toxicity of DON is attributed to mitochondrial dysfunction as a critical factor. Mitochondrial dysfunction characterized by failure in respiratory capacities and ROS overproduction has been demonstrated in intestinal cells exposed to DON. Perturbation of mitochondrial respiration leading to ROS accumulation is implicated in the early initiation of apoptosis. DON-induced intestinal inflammatory response is tightly linked to the mitochondrial ROS, whereas immunosuppression is intimately associated with mitophagy inhibition. DON perturbs the orchestrated bidirectional cross-talk between gut microbe and host mitochondria, which may be involved in DON-induced intestinal toxicity.

Keywords: Apoptosis; Deoxynivalenol; Intestinal toxicity; Microbiota; Mitochondria.