Since ambient particulate matter (APM) is closely related to cardiovascular damage with mitochondria being its potential targets, this study was designed to explore the impact of APM on mitochondrial homeostasis, especially on mitochondrial dynamics and biogenesis in human vascular endothelial cells, using a kind of standard material, PM SRM1648a. As a result, internalized particles lead to mitochondrial dysfunction in EA.hy926 human endothelial cells, including mitochondrial reactive oxygen species (mtROS) overproduction, mitochondrial membrane potential (MMP) reduction and adenosine triphosphate (ATP) inhibition, coupled with additional release of mitochondrial DNA (mtDNA) into the cytosol. Moreover, morpholo... More
Since ambient particulate matter (APM) is closely related to cardiovascular damage with mitochondria being its potential targets, this study was designed to explore the impact of APM on mitochondrial homeostasis, especially on mitochondrial dynamics and biogenesis in human vascular endothelial cells, using a kind of standard material, PM SRM1648a. As a result, internalized particles lead to mitochondrial dysfunction in EA.hy926 human endothelial cells, including mitochondrial reactive oxygen species (mtROS) overproduction, mitochondrial membrane potential (MMP) reduction and adenosine triphosphate (ATP) inhibition, coupled with additional release of mitochondrial DNA (mtDNA) into the cytosol. Moreover, morphological and structural changes in mitochondria are observed in response to PM SRM1648a. In that aspect, according to the evidence of shorter fragmented mitochondria dispersed throughout the cytoplasm, along with aberrant upregulation of fission-related mRNAs/proteins, the mitochondria exhibit a fission phenotype shifting from intact reticular network to fragmentized dotted shapes. Mechanistically, PM SRM1648a facilitates phosphorylation of DRP1 at Ser616 in HUVECs, and triggers its dephosphorylation at Ser637 residue in both EA.hy926 and HUVECs, which are supportive events for mitochondrial fission during particle exposure. Additionally, suppression of a master energy modulator, PGC-1α, reveals that PM SRM1648a has the ability to impair mitochondrial biogenesis. Collectively, it could be well concluded that PM SRM1648a interferes with the equilibrium of mitochondrial dynamics and biogenesis, which is likely to play a pivotal role in mitochondrial dysfunction driven by particles, eventually contributing to endothelial cell damage. Of note, it is more reasonable to conduct risk assessment from both cellular level and subcellular structures, among which mitochondria-targeted toxicity supplements a more comprehensive understanding of APM inducible vascular toxicity.
