Baoxin Qiao ^{a c #}, Panjing Hong ^{a c #}, Ying He ^{b #}, Yumeng Li ^{a c}, Xudong Han ^{a c}, Yanli You ^d, Gaolong Zhong ^{a c}, Zhaoxin Tang ^{a c} *, Lianmei Hu ^{a c} *

       a College of Veterinary Medicine, South China Agricultural University, Guangzhou 510642, China

       b Guangxi Veterinary Research Institute, Nanning 530001, China

       c Key Laboratory of Animal Vaccine Development, Ministry of Agriculture and Rural Affairs, PR China, Guangzhou 510642, China

       d College of Life Science, Yantai University, Yantai 264005, China*Correspondenc

       #These authors have contributed equally to this work.

       ABSTRACT：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.

       Keywords： Arsenic, Lysosomal damage, Calcium transport, Autophagy inhibition

Journal of Environmental Sciences Available online 26 December 2025

       doi：doi.org/10.1016/j.jes.2025.12.071