Ammonium chloride, an environmental pollutant, disrupts melanocyte biology through the regulation of melanosome and autophagy

Ammonium chloride is an indoor environmental pollutant released due to industrial emissions, concrete, indoor bacteria, or other sources. In this study, we characterized molecular mechanisms of ammonium chloride-induced cell damage in melanocyte cells, which are a critical effector for pigmentation. Specifically, we investigated the effects of ammonium chloride on pigmentation and its underlying mechanisms, including its involvement in melanogenesis and autophagy. Based on the experiments, we elucidated that ammonium chloride induced and increased melanogenesis by upregulating MITF via AKT-mediated melanogenic signaling pathways. Moreover, ammonium chloride did not exhibit lysosomotropic activity and inhibited autophagy by activating the AKT-mTOR signaling pathway, suggesting that the pigment-regulating mechanism of ammonium chloride was associated with autophagy in pigmented cells. The findings of this study offer new perspectives on the mechanisms involved in ammonium chloride-induced pigmentation and propose a potential approach to mitigate ammonium chloride-induced side effects like hyperpigmentation and hyperammonemia by employing a combined autophagy inducer.