Crosstalk between Mfn2-mediated mitochondria associated membranes disorder and autophagy induced by molybdenum and cadmium in sheep heart

To investigate the crosstalk of mitochondria associated membranes (MAMs) disorder and autophagy co-induced by molybdenum (Mo) and cadmium (Cd) in sheep hearts. A total of 48 sheep were randomly divided into 4 groups: control group, Mo group, Cd group and Mo + Cd group. The intragastric administration lasted for 50 days. The results showed that Mo or/and Cd exposure could cause morphological damage, imbalance of trace elements and antioxidant function, Ca2+ concentration decreased markedly, and significantly increase the contents of Mo or/and Cd in myocardium. Additionally, the mRNA and protein levels of endoplasmic reticulum stress (ERS) related factors and mitochondrial biogenesis related factors were altered by Mo or/and Cd, as well as the content of ATP, inducing ERS and mitochondrial dysfunction. Meanwhile, Mo or/and Cd could lead to the alteration of expression level of MAMs-related genes and proteins, and the distance between mitochondria and endoplasmic reticulum (ER), resulting in MAMs disorder. Moreover, Mo or/and Cd exposure upregulated the mRNA and protein levels of autophagy related factors. In conclusion, our results revealed that Mo or/and Cd exposure caused ERS, mitochondrial dysfunction and structural MAMs disruption, ultimately leading to autophagy in sheep hearts, and the effects of Mo and Cd co-exposure were more obvious. [Display omitted] •The joint toxicity of Mo and Cd was assessed in sheep myocardial cell.•There was a synergistic effect between non-equitoxic binary mixture of Mo and Cd.•Mo or/and Cd induced disorder of MAMs through Mfn2 pathway.•Mo or/and Cd induced autophagy, which may be associated with MAMs.