Deoxynivalenol Induces Drp-1-Mediated Mitochondrial Dysfunction via Elevating Oxidative Stress.

Area of Science:

• Neuroscience
• Toxicology
• Cell Biology

Background:

• Mitochondrial dysfunction and oxidative stress are implicated in neurotoxicity and neurological diseases.
• Deoxynivalenol (DON), a common mycotoxin, contaminates food and feed, posing health risks.
• Comprehensive studies linking DON to neurodegenerative disorders are limited.

Purpose of the Study:

• To investigate the role of DON in mitochondrial dynamics and cell death in neuronal cells.
• To elucidate the mechanisms of DON-induced neurotoxicity.
• To explore potential therapeutic targets for mycotoxin-induced neurodegeneration.

Main Methods:

• Human SH-SY5Y neuronal cells were treated with varying concentrations of DON.
• Assessed reactive oxygen species (ROS) generation, ATP levels, mitochondrial membrane potential, calcium levels, and cytotoxicity.
• Analyzed the expression of mitochondrial fission/fusion proteins (P-Drp-1, Mff, Fis-1, MFN1, MFN2, OPA1) and autophagy markers (LC3, beclin-1).

Main Results:

• DON exposure dose-dependently increased cytotoxicity, ROS, and intracellular calcium.
• DON treatment decreased ATP levels and mitochondrial membrane potential.
• DON elevated mitochondrial fission proteins (P-Drp-1, Mff, Fis-1) and autophagy markers, while reducing fusion proteins (MFN1, MFN2, OPA1).
• ROS and Ca2+ signaling pathways were confirmed to mediate DON-induced Drp1 phosphorylation.

Conclusions:

• DON induces mitochondrial dysfunction and cell death in neuronal cells via increased oxidative stress and excessive mitochondrial fission.
• ROS and calcium signaling are critical mediators of DON's neurotoxic effects.
• Inhibitors of ROS and mitochondrial fission present potential therapeutic avenues for mycotoxin-induced neurodegenerative diseases.