The transcription factor p8 regulates autophagy during diapause embryo formation in Artemia parthenogenetica

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.

Mechanisms of Desiccation Tolerance: Themes and Variations in Brine Shrimp, Roundworms, and Tardigrades

“…Hsf1 is one transcription factor that can serve as a regulator of the desiccation response, but there are likely other regulators (transcriptional and post-transcriptional) that are involved. It is further possible that transcriptional co-activators like p8 may provide specificity to the transcriptional initiation of diapause and desiccation resistance Lin et al, 2016).…”

Early Molecular Events during Onset of Diapause in Silkworm Eggs Revealed by Transcriptome Analysis

“…Previous studies have identified the core autophagy-related genes (ATGs): ATG8 protein homologs accumulate in starved C. elegans , including dauer larvae and aging adults [ 35 ]. However, in Artemia parthenogenetica , autophagy levels decrease drastically in diapause embryos, and the protein levels of ATG5 and ATG8 are downregulated [ 36 ]. While some researchers proposed that autophagy is upregulated to fulfil the energy requirements for survival by nutrient recycling [ 37 ], others have suggested that, under some conditions, cell cycle arrest is associated with reduced autophagy [ 38 ].…”

Comparative proteomics provides insights into diapause program of Bactrocera minax (Diptera: Tephritidae)

“…To date, the direct evidence for linkage between autophagy and insect diapause is still scarce. However, autophagy has been demonstrated to play roles in the diapause process of other organisms, such as crustacean Artemia parthenogenetica [ 55 ] and harvestmen Amilenus aurantiacus [ 56 ]. Therefore, it is very interesting to consider that autophagy plays a role in insect diapause, which necessitates further verification.…”