Copper is an essential yet toxic metal and its overload causes Wilson disease, a disorder due to mutations in copper transporter ATP7B. To remove excess copper into the bile, ATP7B traffics toward canalicular area of hepatocytes. However, the trafficking mechanisms of ATP7B remain elusive. Here, we show that, in response to elevated copper, ATP7B moves from the Golgi to lysosomes and imports metal into their lumen. ATP7B enables lysosomes to undergo exocytosis through the interaction with p62 subunit of dynactin that allows lysosome translocation toward the canalicular pole of hepatocytes. Activation of lysosomal exocytosis stimulates copper clearance from the hepatocytes and rescues the most frequent Wilson-disease-causing ATP7B mutant to the appropriate functional site. Our findings indicate that lysosomes serve as an important intermediate in ATP7B trafficking, whereas lysosomal exocytosis operates as an integral process in copper excretion and hence can be targeted for therapeutic approaches to combat Wilson disease.

In the last decade or so, polychlorinated biphenyls (PCBs) garnered renewed attention in the scientific community due to new evidence pointing at their continued presence in the environment and workplaces and the potential human risks related to their presence. PCBs move from the environment to humans through different routes; the dominant pathway is the ingestion of contaminated foods (fish, seafood and dairy products), followed by inhalation (both indoor and outdoor air), and, to a lesser extent, dust ingestion and dermal contact. Numerous studies reported the environmental and occupational exposure to these pollutants, deriving from building materials (flame-retardants, plasticizers, paints, caulking compounds, sealants, fluorescent light ballasts, etc.) and electrical equipment. The highest PCBs contaminations were detected in e-waste recycling sites, suggesting the need for the implementation of remediation strategies of such polluted areas to safeguard the health of workers and local populations. Furthermore, a significant correlation between PCB exposure and increased blood PCB concentrations was observed in people working in PCB-contaminated workplaces. Several epidemiological studies suggest that environmental and occupational exposure to high concentrations of PCBs is associated with different health outcomes, such as neuropsychological and neurobehavioral deficits, dementia, immune system dysfunctions, cardiovascular diseases and cancer. In addition, recent studies indicate that PCBs bioaccumulation can reduce fertility, with harmful effects on the reproductive system that can be passed to offspring. In the near future, further studies are needed to assess the real effects of PCBs exposure at low concentrations for prolonged exposure in workplaces and specific indoor environments.

Polycyclic aromatic hydrocarbons (PAHs) are a group of organic compounds with fused aromatic rings, primarily derived from combustion processes and environmental pollutants. This narrative review discusses the most relevant studies on PAHs, focusing on their sources, environmental and occupational exposure, and effects on human health, emphasizing their roles as carcinogenic, mutagenic, and teratogenic agents. The primary pathways for human exposure to PAHs are through the ingestion of contaminated food (mainly due to some food processing methods, such as smoking and high-temperature cooking techniques), the inhalation of ambient air, and the smoking of cigarettes. Coke oven workers are recognized as a high-risk occupational group for PAH exposure, highlighting the need for appropriate strategies to mitigate these risks and safeguard worker health. PAHs are metabolized into reactive intermediates in the body, which can lead to DNA damage and promote the development of various health conditions, particularly in environments with high exposure levels. Chronic PAH exposure has been linked to respiratory diseases, as well as cardiovascular problems and immune system suppression. Furthermore, this review underscores the significant impact of PAHs on reproductive health. The results of the reported studies suggest that both male and female fertility can be compromised due to oxidative stress, DNA damage, and endocrine disruption caused by PAH exposure. In males, PAHs impair sperm quality, while, in females, they disrupt ovarian function, potentially leading to infertility, miscarriage, and birth defects. Fetal exposure to PAHs is also associated with neurodevelopmental disorders. Given the extensive and detrimental health risks posed by PAHs, this review stresses the importance of stringent environmental regulations, occupational safety measures, and public health initiatives to mitigate exposure and safeguard reproductive and overall health.