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Apoptosis

pp 1–16 | Cite as

Klotho-mediated changes in the expression of Atg13 alter formation of ULK1 complex and thus initiation of ER- and Golgi-stress response mediated autophagy

  • Jennifer MytychEmail author
  • Przemysław Sołek
  • Agnieszka Będzińska
  • Kinga Rusinek
  • Aleksandra Warzybok
  • Anna Tabęcka-Łonczyńska
  • Marek Koziorowski
Article
  • 108 Downloads

Abstract

In the previous paper of our group, we have demonstrated that one of the crucial factors involved in the crosstalk between autophagy and apoptosis is klotho protein. We have shown that klotho silencing in normal human fibroblasts intensifies lipopolysaccharide (LPS)-induced p-eIF2a-mediated stress of endoplasmic reticulum and thus leads to retardation of prosurvival autophagy and induction of apoptotic cell death. In this study, we have performed a detailed step-by-step analysis of autophagy flux-related genes’ expression and endoplasmic reticulum and Golgi stress related pathways in order to determine the exact mechanistic event when autophagy is inhibited in klotho-deficient cells on account of apoptosis initiation. We provide evidence that klotho-silencing in LPS-treated cells results in differential course of ER- and Golgi-mediated stress response. Further, we show that in klotho-deficient cells formation of ULK1 complex is inhibited and thus autophagy initiation is blocked on the account of apoptosis activation, while in the control cells cytoprotective autophagy is activated. Finally, in klotho-deficient cells formation of ULK1 complex is prevented by downregulated expression of Atg13. Thus, this study suggests a novel targeting pathway for efficient elimination of autophagy-deficient cells.

Keywords

Klotho Autophagy ER stress response Golgi stress response 

Notes

Authors’ contribution

JM, PS, AB, KR, AW, AT-L: performed the experiments, JM, PS: analyzed the data, JM, PS, MK carried out data interpretation, JM: wrote the paper, JM: conceived and designed the experiments. AB, KR, AW are students of Biotechnology at University of Rzeszow.

Funding

This work was supported by the “Miniatura” No. DEC-2018/02/X/NZ3/00729 funded by the Polish National Science Center.

Compliance with ethical standards

Conflict of interest

There is no conflict of interest.

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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Department of Animal Physiology and Reproduction, Faculty of BiotechnologyUniversity of RzeszowKolbuszowaPoland

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