Arsenic induces chicken liver injury by inhibiting endoplasmic reticulum-lysosomal calcium ion transport and lysosomal autophagy activity via the IP3R/TRPML1 pathway.

Arsenic is a toxic substance widely present in the environment, and arsenic-containing pesticides and fertilizers are widely used in agricultural production. However, arsenic can enter the human body through the food chain, posing a serious threat to human health. The liver is an important metabolic and detoxification organ in living organisms and is particularly vulnerable to exogenous toxins. Transient receptor potential mucolipin 1 (TRPML1) and Inositol 1,4,5-trisphosphate receptor (IP3R), as calcium-transporting proteins on cellular organelles, play key roles in maintaining intracellular calcium homeostasis as well as organelle function and cell signaling. However, studies on the mechanism of intracellular calcium signaling in arsenic-induced liver injury are lacking. We found that arsenic impeded the endoplasmic reticulum-lysosome calcium transport process and induced impaired lysosomal activity and lysosome-associated autophagy blockage through this pathway, which ultimately led to chicken liver injury. Notably, TRPML1 and IP3R proteins are key proteins involved in the above process. This study demonstrates that arsenic induces calcium transport disruption between the endoplasmic reticulum and lysosomes via TRPML1 and IP3R proteins. This disruption impairs lysosomal function and blocks autophagy. Furthermore, this represents the first validation of this mechanism in a chicken model, offering new insights into investigating the risks of environmental arsenic exposure to human health.