Toxalim (Research Centre in Food Toxicology), Université de Toulouse, INRAE, ENVT, INP-Purpan, UPS, Toulouse, France.
Published: October 2023
AI Article Synopsis
Article Abstract
Ribosomes that synthesize proteins are among the most central and evolutionarily conserved organelles. Given the key role of proteins in cellular functions, prokaryotic and eukaryotic pathogens have evolved potent toxins to inhibit ribosomal functions and weaken their host. Many of these ribotoxin-producing pathogens are associated with food. For example, food can be contaminated with bacterial pathogens that produce the ribotoxin Shiga toxin, but also with the fungal ribotoxin deoxynivalenol. Shiga toxin cleaves ribosomal RNA, while deoxynivalenol binds to and inhibits the peptidyl transferase center. Despite their distinct modes of action, both groups of ribotoxins hinder protein translation, but also trigger other comparable toxic effects, which depend or not on the activation of the ribotoxic stress response. Ribotoxic stress response-dependent effects include inflammation and apoptosis, whereas ribotoxic stress response-independent effects include endoplasmic reticulum stress, oxidative stress, and autophagy. For other effects, such as cell cycle arrest and cytoskeleton modulation, the involvement of the ribotoxic stress response is still controversial. Ribotoxins affect one organelle yet induce multiple toxic effects with multiple consequences for the cell. The ribosome can therefore be considered as the cellular "Achilles heel" targeted by food borne ribotoxins. Considering the high toxicity of ribotoxins, they pose a substantial health risk, as humans are highly susceptible to widespread exposure to these toxins through contaminated food sources.
Center for Gene Expression, Department of Cellular and Molecular Medicine, University of Copenhagen, Blegdamsvej 3B, DK-2200 Copenhagen, Denmark. Electronic address:
Next to their essential role as protein production factories, ribosomes serve as molecular sensors of cell stress. Stalled and collided ribosomes trigger specific stress signaling, including the ribotoxic stress response (RSR). The RSR is initiated by the mitogen-activated protein (MAP)-3 kinase ZAKα in response to a plethora of translational aberrations, leading to activation of the stress-activated MAP kinases p38 and jun N-terminal kinase (JNK).
Center for Healthy Aging, Department of Cellular and Molecular Medicine, University of Copenhagen, Blegdamsvej 3, 2200 Copenhagen, Denmark; Center for Gene Expression, Department of Cellular and Molecular Medicine, University of Copenhagen, Blegdamsvej 3, 2200 Copenhagen, Denmark. Electronic address:
Solar UVB light causes damage to the outermost layer of skin. This insult induces rapid local responses, such as dermal inflammation, keratinocyte cell death, and epidermal thickening, all of which have traditionally been associated with DNA damage response signaling. Another stress response that is activated by UVB light is the ribotoxic stress response (RSR), which depends on the ribosome-associated mitogen-activated protein 3 kinases (MAP3K) ZAKα and culminates in p38 and JNK activation.
* This study focused on the interaction between two significant mycotoxins: aflatoxin B1 (AFB1), a strong carcinogen, and deoxynivalenol (DON), which is commonly found in food.
* Findings reveal that DON reduces the harmful effects of AFB1 by inhibiting the activity of enzymes that activate AFB1, suggesting the need to study these toxins together rather than in isolation.
Metabolic stress must be effectively mitigated for the survival of cells and organisms. Ribosomes have emerged as signaling hubs that sense metabolic perturbations and coordinate responses that either restore homeostasis or trigger cell death. As yet, the mechanisms governing these cell fate decisions are not well understood.
