TY - JOUR
T1 - Intercellular transfer of mitochondria via tunneling nanotubes protects against cobalt nanoparticle-induced neurotoxicity and mitochondrial damage
AU - Zheng, Fuli
AU - Luo, Zhousong
AU - Lin, Xinpei
AU - Wang, Wei
AU - Aschner, Michael
AU - Cai, Ping
AU - Wang, Yuan Liang
AU - Shao, Wenya
AU - Yu, Guangxia
AU - Guo, Zhenkun
AU - Wu, Siying
AU - Li, Huangyuan
N1 - Publisher Copyright:
© 2022 Informa UK Limited, trading as Taylor & Francis Group.
PY - 2021
Y1 - 2021
N2 - 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.
AB - 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.
KW - Cobalt nanoparticles (CoNPs)
KW - astrocytes
KW - mitochondrial transfer
KW - neurotoxicity
KW - tunneling nanotubes (TNTs)
UR - http://www.scopus.com/inward/record.url?scp=85123466848&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85123466848&partnerID=8YFLogxK
U2 - 10.1080/17435390.2022.2026515
DO - 10.1080/17435390.2022.2026515
M3 - Article
C2 - 35077651
AN - SCOPUS:85123466848
SN - 1743-5390
VL - 15
SP - 1358
EP - 1379
JO - Nanotoxicology
JF - Nanotoxicology
IS - 10
ER -