Multi-walled carbon nanotubes upregulate mitochondrial gene expression and trigger mitochondrial dysfunction in...

Area of Science:

• Nanotoxicology
• Cell Biology
• Mitochondrial Biology

Background:

• Nanomaterials, like carbon nanotubes, offer novel properties but pose potential health risks.
• Carbon nanotubes (CNTs) are widely used and can be inhaled, leading to potential cellular exposure.
• While CNTs' nuclear DNA effects are known, their impact on mitochondrial DNA (mtDNA) is less understood.

Purpose of the Study:

• To investigate the effects of multi-walled carbon nanotubes (MWCNTs) on mitochondrial gene expression and function.
• To assess MWCNT-induced changes in human bronchial epithelial cells (BECs), focusing on mitochondrial health.

Main Methods:

• Primary BECs were exposed to sub-cytotoxic doses of MWCNTs for 5 days.
• Assessed mitochondrial gene expression, mtDNA heteroplasmies, and insertion/deletion mutations (indels).
• Measured cytotoxicity, metabolic function, mitochondrial abundance, and mitophagy.

Main Results:

• MWCNTs upregulated mitochondrial gene expression but decreased oxygen consumption rate and mitochondrial abundance.
• Mitophagy was induced within 2 hours of MWCNT exposure.
• No significant effects on mtDNA heteroplasmy or indel mutations were observed.

Conclusions:

• MWCNTs induce mitochondrial dysfunction in human bronchial epithelial cells.
• This dysfunction triggers mitophagy, a cellular response to remove damaged mitochondria.
• The mechanism of MWCNT-induced mitochondrial impairment is independent of genotoxicity to mtDNA.