Deficiency of hepatocystin induces autophagy through an mTOR-dependent pathway

Jing Yang, Ying Zhao, Ke Ma, Fen-Jun Jiang, Wenjuan Liao, Ping Zhang, Jingyi Zhou, Bo Tu, Lina Wang, Harm H. Kampinga, Zhiping Xie*, Wei-Guo Zhu

*Bijbehorende auteur voor dit werk

    OnderzoeksoutputAcademicpeer review

    16 Citaten (Scopus)


    Mutations in the gene encoding hepatocystin/80K-H (PRKCSH) cause autosomal-dominant polycystic liver disease (ADPLD). Hepatocystin functions in the processing of nascent glycoproteins as the noncatalytic beta subunit of glucosidase II (Glu II) and regulates calcium release from endoplasmic reticulum (ER) through the inositol-1,4,5-trisphosphate receptor (IP3R). Little is known, however, on how cells respond to a deficiency of hepatocystin. In this study, we demonstrate that knockdown of hepatocystin induces autophagy, the major intracellular degradation pathway essential for cellular health. Ectopic expression of wild-type hepatocystin, but not pathogenic mutants, rescues the siRNA-induced effect. Our data indicate that the induction of autophagy by hepatocystin deficiency is mediated through mammalian target of rapamycin (mTOR). Despite the resulting severe reduction in Glu II activity, the unfolded protein response (UPR) pathway is not disturbed. Furthermore, the inhibition of IP3R-mediated transient calcium flux is not required for the induction of autophagy. These results provide new insights into the function of hepatocysin and the regulation of autophagy.

    Originele taal-2English
    Pagina's (van-tot)748-759
    Aantal pagina's12
    Nummer van het tijdschrift7
    StatusPublished - jul-2011

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