Multi-walled carbon nanotubes upregulate mitochondrial gene expression and trigger mitochondrial dysfunction in primary human bronchial epithelial cells

Ryan J. Snyder, Kirsten C. Verhein, Heather L. Vellers, Adam B. Burkholder, Stavros Garantziotis, Steven R. Kleeberger

Research output: Contribution to journalArticlepeer-review

3 Scopus citations

Abstract

Nanomaterials are a relatively new class of materials that acquire novel properties based on their reduced size. While these materials have widespread use in consumer products and industrial applications, the potential health risks associated with exposure to them remain to be fully characterized. Carbon nanotubes are among the most widely used nanomaterials and have high potential for human exposure by inhalation. These nanomaterials are known to penetrate the cell membrane and interact with intracellular molecules, resulting in a multitude of documented effects, including oxidative stress, genotoxicity, impaired metabolism, and apoptosis. While the capacity for carbon nanotubes to damage nuclear DNA has been established, the effect of exposure on mitochondrial DNA (mtDNA) is relatively unexplored. In this study, we investigated the potential of multi-walled carbon nanotubes (MWCNTs) to impair mitochondrial gene expression and function in human bronchial epithelial cells (BECs). Primary BECs were exposed to sub-cytotoxic doses (up to 3 μg/ml) of MWCNTs for 5 d and assessed for changes in expression of all mitochondrial protein-coding genes, heteroplasmies, and insertion/deletion mutations (indels). Exposed cells were also measured for cytotoxicity, metabolic function, mitochondrial abundance, and mitophagy. We found that MWCNTs upregulated mitochondrial gene expression, while significantly decreasing oxygen consumption rate and mitochondrial abundance. Confocal microscopy revealed induction of mitophagy by 2 hours of exposure. Mitochondrial DNA heteroplasmy and insertion/deletion mutations were not significantly affected by any treatment. We conclude that carbon nanotubes cause mitochondrial dysfunction that leads to mitophagy in exposed BECs via a mechanism unrelated to its reported genotoxicity.

Original languageEnglish
Pages (from-to)1344-1361
Number of pages18
JournalNanotoxicology
Volume13
Issue number10
DOIs
StatePublished - Nov 26 2019

Keywords

  • Carbon nanotubes
  • epithelial
  • genotoxicity
  • in vitro
  • mitochondria

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