Impairment of mitochondrial dynamics involved in iron oxide nanoparticle-induced dysfunction of dendritic cells was alleviated by autophagy inhibitor 3-methyladenine.

Iron oxide nanoparticles are nanomaterials that are used extensively in the biomedical field, but they are associated with adverse effects, including mitochondrial toxicity. Mitochondrial homeostasis is achieved through dynamic stability based on two sets of antagonistic balanced processes: mitochondrial biogenesis and degradation as well as mitochondrial fission and fusion. In this study, we showed that PEG-COOH-coated Fe O (PEG-Fe O ) nanoparticles induced mitochondrial instability in dendritic cells (DCs) by impairing mitochondrial dynamics due to promotion of mitochondrial biogenesis through activation of the peroxisome proliferator-activated receptor γ coactivator 1α (PGC1α) pathway, inhibiting mitochondrial degradation via decreased autophagy, and facilitating mitochondrial fragmentation involving increased levels of DRP1 and MFN2. The resulting reduced levels of dextran uptake, CD80, CD86 and chemokine receptor 7 (CCR7) suggested that PEG-Fe O nanoparticles impaired the functionally immature state of DCs. Autophagy inhibitor 3-methyladenine (3-MA) alleviated PEG-Fe O nanoparticle-induced mitochondrial instability and impairment of the functionally immature state of DCs due to unexpected enhancement of PGC1α/MFN2-mediated coordination of mitochondrial biogenesis and fusion.