Acrylamide Induces Abnormal mtDNA Expression by Causing Mitochondrial ROS Accumulation, Biogenesis, and Dynamics...

Area of Science:

• Neuroscience
• Toxicology
• Cell Biology

Background:

• Acrylamide is a neurotoxicant found in cooked foods.
• Acrylamide-induced apoptosis and mitochondrial dysfunction contribute to neurotoxicity.
• The precise mechanisms of acrylamide's mitochondrial impairment remain unclear.

Purpose of the Study:

• To elucidate the mechanisms by which acrylamide causes mitochondrial impairment and neurotoxicity.
• To investigate the role of mitochondrial reactive oxygen species (ROS) in acrylamide neurotoxicity.
• To evaluate the protective effects of a mitochondrial ROS scavenger against acrylamide-induced damage.

Main Methods:

• Astrocytes were treated with acrylamide to observe cellular and mitochondrial changes.
• Gene expression analysis was performed for mitochondrial biogenesis and dynamics markers (PGC-1α, TFAM, Mfn2, Opa1) and mtDNA-encoded respiratory chain complexes.
• Mitochondrial respiration and ROS levels were measured.
• In vivo experiments in rat brain tissues were conducted.
• Mitoquinone, a ROS scavenger, was used for pretreatment studies.

Main Results:

• Acrylamide treatment in astrocytes led to destroyed redox balance, increased mitochondrial ROS, damaged mitochondrial structures, and activated apoptosis.
• Acrylamide decreased the expression of PGC-1α, TFAM, Mfn2, and Opa1, and inhibited mitochondrial respiration.
• Mitoquinone pretreatment restored gene expression, protected mitochondrial structure, and reduced apoptosis.
• In vivo studies confirmed acrylamide's down-regulation of PGC-1α, TFAM, Mfn2, and Opa1 in rat brains.

Conclusions:

• Acrylamide triggers mitochondrial ROS accumulation, which interferes with mitochondrial biogenesis and dynamics.
• This interference leads to mtDNA damage, mitochondrial dysfunction, and ultimately apoptosis.
• Targeting mitochondrial ROS may offer a therapeutic strategy against acrylamide neurotoxicity.