Exposure to environmental contaminants (Polychlorinated biphenyls) affects mitochondrial plasticity in murine neuroblastoma cells

Polychlorinated biphenyls (PCBs), widely used in a variety of industrial and consumer products for several decades, were banned in the 1970s. Due to their extensive industrial use and chemical stability,however,  PCBs are still ubiquitous and persistent environmental contaminants. Although clear evidence of a correlation between neurological damage and PCB exposure has been widely described, the molecular and cellular mechanisms involved in these changes require further in depth assessments. This study aims to determine whether exposure to PCBs is capable of causing changes in mitochondrial dynamics and influence neuronal physiology and survival. In the present work, mouse neuroblastoma cell line (Neuro2a) was exposed to a environmentally relevant mixture of PCBs and effects on mitochondrial quality control and plasticity were analyzed as a proxy of a neurodegenerative process. MTT assays were performed to investigate cell viability, while RT-qPCR and western blot were employed for the analysis of genes and proteins related to mitochondrial fission, fusion and biogenesis. Immunofluorescence, electron microscopy and mtDNA assays were also performed. Despite not promoting changes in cell viability, exposure to PCBs alters mitochondrial dynamics. Mitofusins (Mfn) -1 and -2 and Optic atrophy 1 (OPA1) markers of mitochondrial fusion were investigated by RT-qPCR. A 2-fold increase in Mfn1 at 72 hours of exposure was observed. Among the mitochondrial fission markers evaluated, a significant increase in Fis1 and Drp1 (1.8- and 1.5-fold increase, respectively) after 24 hours of exposure. We also observed an increase in TOMM20 and PINK-1 (1.4- and 2-fold increase, respectively), related to mitochondrial biogenesis and degradation; a sustained increase in ATG5 (1.2-fold) transcripts was observed at all exposure times. Taken together, these findings shed light on the mechanisms through which PCBs can lead to abnormal cell functioning and fate.