Nickel induces hepatotoxicity by mitochondrial biogenesis, mitochondrial dynamics, and mitophagy dysfunction

Area of Science:

• Toxicology
• Cell Biology
• Biochemistry

Background:

• Nickel (Ni) is a hazardous industrial waste causing multi-organ toxicity.
• The liver is a primary target for Ni accumulation and toxicity, but mechanisms remain unclear.

Purpose of the Study:

• To investigate the precise molecular mechanisms of nickel chloride (NiCl2)-induced hepatotoxicity.
• To examine the effects of NiCl2 on mitochondrial biogenesis, dynamics, and mitophagy in mouse liver.

Main Methods:

• Mice were treated with nickel chloride (NiCl2).
• Hepatic histopathology and transmission electron microscopy were performed.
• Mitochondrial biogenesis, dynamics (fusion/fission), and mitophagy markers were analyzed via protein and mRNA expression.

Main Results:

• NiCl2 induced hepatic histopathological changes and mitochondrial damage (swelling, deformation).
• NiCl2 suppressed mitochondrial biogenesis (decreased PGC-1α, TFAM, NRF1) and altered mitochondrial dynamics (reduced fusion proteins Mfn1/Mfn2, increased fission proteins Drip1/Fis1).
• NiCl2 upregulated mitophagy markers (p62, LC3II, PINK1, Parkin, Bnip3, FUNDC1), indicating enhanced mitophagy.

Conclusions:

• NiCl2 induces liver damage in mice through mitochondrial dysfunction.
• Disrupted mitochondrial biogenesis, dynamics, and mitophagy are key molecular mechanisms underlying NiCl2-induced hepatotoxicity.