Research identifies PGAM5 as a key target in lycopene-mediated protection against gut toxin damage

Fungal toxins contaminating food and animal feed pose a major threat to livestock health. In particular, deoxynivalenol (DON), a toxin produced by Fusarium fungi, can severely damage pig gut cells. A recent study in China reveals that lycopene, a natural antioxidant derived from tomatoes, helps protect these cells from DON-induced injury. It does so by blocking PGAM5, a key protein involved in cellular stress—-highlighting its potential in preventing toxin-related damage.

Agricultural and feed industries are growing rapidly worldwide, yet contamination by fungal toxins remains a major concern, affecting both food safety and livestock health. One of the major contributors to this problem is deoxynivalenol (DON), a fungal toxin produced by Fusarium fungi that frequently infects cereal crops such as wheat and maize. Farm animals, especially pigs, are particularly vulnerable to DON exposure, which can damage the intestinal lining, impair nutrient absorption, and weaken immune functions.

To combat this issue, a recent study conducted at Northeast Agricultural University, China, led by Associate Professor Yi Zhao from Northeast Agricultural University, China, revealed that lycopene, a natural antioxidant pigment found in tomatoes and other red fruits, can protect intestinal cells from DON-induced damage. The study, published online in Research on March 25, 2026, provides new insights into how natural dietary compounds may be used to combat the harmful effects of fungal toxins.

Intestinal epithelial cells (lining the surface of intestines) serve as a protective barrier, preventing harmful substances, pathogens and toxins from entering the bloodstream while allowing the absorption of nutrients. If this barrier is damaged, it can lead to inflammation, poor digestion, and increased susceptibility to disease.

“DON can severely disrupt this barrier in porcine intestinal epithelial cells by reducing cell viability, impairing movement, and disrupting cell structure,” explains Dr. Zhao.
It does this by triggering a harmful chain of events inside the cells. One significant effect is mitophagy, a natural cellular recycling mechanism in which damaged mitochondria (the cell’s energy-producing structures) are removed. DON causes overactive mitophagy, leading to mitochondrial dysfunction and cellular stress. Simultaneously, the toxin also induces ferroptosis, a specialized form of programmed cell death driven by iron accumulation and damage to membrane lipids, associated with iron-dependent oxidative damage.
The researchers observed that when cells were exposed to DON, they exhibited increased levels of reactive oxygen species (ROS), leading to oxidative stress, elevated lipid peroxidation, and iron ion accumulation. Altogether, these changes contributed to severe barrier injury.
However, when the cells were treated with a natural tomato-derived molecule called lycopene, the results were remarkably different. The use of lycopene improved cell survival and restored barrier integrity. It increased the expression of tight junction proteins, including ZO-1, Occludin, Claudin-1, Claudin-5, and E-cadherin, which act as molecular “seals” between adjacent cells and help maintain the strength of the intestinal barrier. Moreover, being an antioxidant, lycopene also reduced ROS levels, leading to stabilized mitochondrial function and restored iron balance within the cells.

“The key regulator behind this process is PGAM5, a protein that controls cellular stress and cell death pathways,” comments Dr. Zhao.
The exposure to DON caused PGAM5 levels to rise significantly, resulting in the activation of the mitochondrial quality control pathway involving PINK1 and PARKIN. These two proteins are responsible for the regulation of mitophagy. Excessive activation of these proteins ultimately promoted ferroptosis and breakdown of the intestinal barrier.
Lycopene suppressed the overexpression of PGAM5 and reduced the activation of downstream pathways. Further support came from molecular docking analysis, a computational method used to predict how molecules interact at the atomic level. The analysis suggested that lycopene directly binds to PGAM5, indicating that this protein may be a direct target of its protective action.

To confirm this mechanism, researchers artificially increased PGAM5 levels in cells. Under these conditions, lycopene lost most of its protective effect, confirming that PGAM5 overexpression overrides its benefits.

Overall, the findings establish a clear mechanism: DON activates PGAM5, driving excessive mitophagy and ferroptosis, which damages the intestinal barrier. Lycopene interrupts this pathway by inhibiting PGAM5, thereby preserving cellular health. These results position lycopene as a promising candidate for protecting against fungal toxin-induced intestinal disorders and highlight its potential for improving livestock health through dietary interventions.

The complete study is accessible via DOI:10.34133/research.1251

About the Journal:
Launched in 2018, Research is the first journal in the Science Partner Journal (SPJ) program. Research is published by the American Association for the Advancement of Science (AAAS) in association with Science and Technology Review Publishing House. Research publishes fundamental research in the life and physical sciences, as well as important findings or issues in engineering and applied science. The journal publishes original research articles, reviews, perspectives, and editorials. It has an impact Factor of 10.7 and a Cite score of 13.3.

Funding information
This work was supported by National Natural Science Foundation of China (Grant No. 32402968), Outstanding Youth of Natural Science Foundation of Heilongjiang Province of China (Grant No. YQ2023C017), Academic Backbone Project of Northeast Agricultural University (Grant No. 54960212), Heilongjiang Postdoctoral Fund (Grant No. LBH-Z23010), Heilongjiang Postdoctoral Special Fund (Grant No. LBH-TZ2404), China Postdoctoral Science Foundation (Grant No. 2023MD744173) and Postdoctoral Special Funding of China (Grant No. 2024T170118).