Journal of hazardous materialsNov 16, 2025

Deoxynivalenol may cause liver damage by blocking protective cell signals through excessive removal of damaged mitochondria

Longevity & Aging Weekly Brief ↗PubMed ↗DOI ↗

Updated Jan 7, 2026

Abstract

Deoxynivalenol (DON) induces liver injury by overactivating mitophagy and inhibiting the p62-Keap1-Nrf2 signaling pathway.

DON treatment in mice and hepatocyte cells leads to mitochondrial damage.
Overactivation of PINK1/Parkin-mediated mitophagy is observed with DON exposure.
This mitophagy overactivation is associated with increased apoptosis, oxidative stress, inflammation, and lipid metabolism disorders.
DON suppresses the p62-Keap1-Nrf2 cytoprotective pathway, weakening cellular defenses.
Overexpression of p62 can reduce liver injury caused by DON by promoting Nrf2 activity.

Simplified

Deoxynivalenol (DON), a prevalent mycotoxin contaminant in food and feed, poses severe threats to both human and animal health. However, the mechanisms underlying DON-induced hepatotoxicity remain unclear. In this research, mice and the immortalized normal mouse hepatocyte cell line (AML-12) were treated with DON at 0 -4.8 mg/kg (7 d) and 0 -6.4 μM (24 h), respectively. Our results indicated that DON induces overactivation of PINK1/Parkin-mediated mitophagy, leading to mitochondrial damage. This activation promotes apoptosis, oxidative stress, inflammation, and lipid metabolism disorder, as confirmed through the use of mitophagy inhibitors (Mdivi-1) and si-PINK1. Moreover, DON simultaneously suppresses the p62-Keap1-Nrf2 cytoprotective pathway, thereby compromising the cellular defense system and amplifying injury. Notably, p62 overexpression mitigates DON-induced liver injury through competitive binding to Keap1, promoting Nrf2 nuclear translocation. Overall, our findings reveal that DON induces liver injury by inhibiting the p62-Keap1-Nrf2 signaling pathway via overactivation of PINK1/Parkin-mediated mitophagy.

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Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

PubMed

Deoxynivalenol may cause liver damage by blocking protective cell signals through excessive removal of damaged mitochondria

Abstract

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Competing interests

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