Intercellular transfer of mitochondria via tunneling nanotubes protects against cobalt nanoparticle-induced neurotoxicity and mitochondrial damage

Fuli Zheng, Zhousong Luo, Xinpei Lin, Wei Wang, Michael Aschner, Ping Cai, Yuan Liang Wang, Wenya Shao, Guangxia Yu, Zhenkun Guo, Siying Wu, Huangyuan Li

Research output: Contribution to journalArticlepeer-review

Abstract

Broad applications of cobalt nanoparticles (CoNPs) have raised increased concerns regarding their potential toxicity. However, the underlining mechanisms of their toxicity have yet to be characterized. Here, we demonstrated that CoNPs reduced cell viability and induced membrane leakage. CoNPs induced oxidative stress, as indicated by the generation of reactive oxygen species (ROS) secondary to the increased expression of hypoxia-induced factor 1 alpha. Moreover, CoNPs led to mitochondrial damage, including generation of mitochondrial ROS, reduction in ATP content, morphological damage and autophagy. Interestingly, exogenous mitochondria were observed between neurons and astrocytes upon CoNPs exposure. Concomitantly, tunneling nanotubes (TNTs)-like structures were observed between neurons and astrocytes upon CoNPs exposure. These structures were further verified to be TNTs as they were found to be F-actin rich and lacking tubulin. We then demonstrated that TNTs were utilized for mitochondrial transfer between neurons and astrocytes, suggesting a novel crosstalk phenomenon between these cells. Moreover, we found that the inhibition of TNTs (using actin-depolymerizing drug latrunculin B) intensified apoptosis triggered by CoNPs. Therefore, we demonstrate, for the first time, that the inhibition of intercellular mitochondrial transfer via TNTs aggravates CoNPs-induced cellular and mitochondrial toxicity in neuronal cells, implying a novel intercellular protection mechanism in response to nanoparticle exposure.

Original languageEnglish (US)
Pages (from-to)1358-1379
Number of pages22
JournalNanotoxicology
Volume15
Issue number10
DOIs
StatePublished - 2021

Keywords

  • Cobalt nanoparticles (CoNPs)
  • astrocytes
  • mitochondrial transfer
  • neurotoxicity
  • tunneling nanotubes (TNTs)

ASJC Scopus subject areas

  • Biomedical Engineering
  • Toxicology

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