LAUSR

Abstract Autophagy acts as important cytoprotective mechanism in response to adverse environment conditions. The hypothesis of the present study is that autophagy acts as protective responses to waterborne Zn exposure. To this end, the full-length cDNA sequences of 12 key genes related to autophagy in yellow catfish Pelteobagrus fulvidraco were cloned, and their mRNA expression profiles and transcriptional responses to waterborne Zn exposure were explored. The 12 genes (SQSTM1, Beclin1, ULK1A, ULK1B, ATG13-1, ATG13-2, ATG101, ATG9A, ATG9B, ATG3, ATG5 and ATG7) mediated the core autophagy machinery, including autophagosome membrane initiation, nucleation, expansion, closure and maturation. All of these members shared similar domain structure to their orthologous genes of other vertebrates. Their mRNAs were widely expressed in various tissues, but at different levels. Zn exposure increased the amount of hepatic autophagic vacuoles, and elevated the mRNA levels of SQSTM1, ULK1A, ULK1B, ATG13, ATG101, ATG9A, ATG9B, ATG3 and ATG7 in a dose- and time-dependent manner, indicating autophagy activation. These results indicated that autophagy acted as an adaptive response to protect from Zn toxicity and confirmed our hypothesis. Moreover, those up-regulated genes may play crucial roles in autophagy response to Zn exposure. For the first time, we characterized the full-length cDNA sequences of twelve autophagy related genes from fish, and determined their transcriptional responses to waterborne Zn exposure, which would contribute to our understanding of the molecular basis of autophagy and Zn toxicity, and also shed new insights on the potential role of autophagy as an adaptive response against metal toxicity in vertebrates.