Cadmium-induced cytotoxicity in mouse liver cells is associated with the disruption of autophagic flux via inhibiting the fusion of autophagosomes and lysosomes

Schematic diagram of Cd-induced autophagy blockade in liver cells. Cd could trigger lysosomal activation, enhance lysosomal degradation capacity, promote autophagy, and inhibit autophagosome-lysosome fusion after entering into liver cells. In addition, Cd could also downregulate the protein expression of Rab7. [Display omitted] •Cadmium could induce cell injury and promote autophagy in liver cells.•Cadmium could induce autophagic flux blockade.•Cadmium could trigger lysosomal activation, and enhance lysosomal degradation.•Cadmium induces autophagic flux blockade by inhibiting autophagosome-lysosome fusion.•Autophagic flux blockade is probably related to the downregulation of Rab7. Cadmium (Cd) is an important environmental pollutant. Previous studies have shown that Cd can induce liver cell injury; however, the toxicity mechanisms of Cd have not been fully elucidated. This study aimed to further confirm the hepatotoxic effects of Cd in mouse liver cells by various methods both in vivo and in vitro. In addition, it found that Cd induced autophagy but also caused autophagy blockade, and autophagy blockade intensified Cd-induced injury in liver cells. Subsequently, the study investigated the effects of Cd on lysosomes and found that Cd induced lysosomal acidification, promoted the expression of lysosomal-associated membrane protein 2 and lysosomal hydrolase cathepsin B both in vivo and in vitro, and enhanced the lysosomal degradation capacity. It indicated that Cd triggered lysosomal activation. However, the fusion of autophagosomes with lysosomes was inhibited by Cd both in vivo and in vitro. Next, the expression of Rab7, a key protein that regulates autophagosome–lysosome fusion, was examined. Cd was found to inhibit Rab7 expression both in vivo and in vitro. In conclusion, the results indicated that Cd obstructed the autophagic flux by inhibiting the fusion of autophagosomes with lysosomes, thus exacerbating the Cd-induced hepatotoxicity. Moreover, the molecular mechanism of Cd-induced inhibition of autophagosome–lysosome fusion is probably related to the Cd-induced downregulation of Rab7.