Abstract
Autophagy is an essential homeostatic process by which cytoplasmic components, including macromolecules and organelles, are degraded by lysosome. Increasing evidence suggests that phosphorylated AMP-activated protein kinase (p-AMPK) and target of rapamycin (TOR) play key roles in the regulation of autophagy. However, the regulation of autophagy in quiescent cells remains unclear, despite the fact that autophagy is known to be critical for normal development, regeneration, and degenerative diseases. Here, crustacean Artemia parthenogenetica was used as a model system because they produced and released encysted embryos that enter a state of obligate dormancy in cell quiescence to withstand various environmental threats. We observed that autophagy was increased before diapause stage but dropped to extremely low level in diapause cysts in Artemia. Western blot analyses indicated that the regulation of autophagy was AMPK/TOR independent during diapause embryo formation. Importantly, the level of p8 (Ar-p8), a stress-inducible transcription cofactor, was elevated at the stage just before diapause and was absent in encysted embryos, indicating that Ar-p8 may regulate autophagy. The results of Ar-p8 knockdown revealed that Ar-p8 regulated autophagy during diapause formation in Artemia. Moreover, we observed that activating transcription factors 4 and 6 (ATF4 and ATF6) responded to Ar-p8-regulated autophagy, indicating that autophagy targeted endoplasmic reticulum (ER) during diapause formation in Artemia. Additionally, AMPK/TOR-independent autophagy was validated in human gastric cancer MKN45 cells overexpressing Ar-p8. The findings presented here may provide insights into the role of p8 in regulating autophagy in quiescent cells.
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Acknowledgments
This work was supported by the National Natural Science Foundation of China (31370394 and 31270424) and the 863 Program of China (2012AA092103).
Author contributions
CL, SNJ, and WJY designed the research; CL, SNJ, FY, WHJ, and XJY performed the work; JSY contributed new reagents/analytical tools; CL and SNJ analyzed the data; and CL, SNJ, and WJY wrote the paper.
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Cheng Lin and Sheng-Nan Jia contributed equally to this work.
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Lin, C., Jia, SN., Yang, F. et al. The transcription factor p8 regulates autophagy during diapause embryo formation in Artemia parthenogenetica . Cell Stress and Chaperones 21, 665–675 (2016). https://doi.org/10.1007/s12192-016-0692-6
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DOI: https://doi.org/10.1007/s12192-016-0692-6