DOR is a bi-functional protein that regulates transcription and enhances starvation-induced autophagy. While autophagy has been mostly described as a stress-response mechanism, cells also need autophagy to maintain homeostasis in basal conditions. However, the mechanisms regulating basal autophagy still remain unknown. Our results show that DOR acts in basal autophagy. Indeed, DOR already undergoes nucleo-cytoplasmic shuttling in basal conditions and, surprisingly, DOR exits continuously the nucleus and traverses the nucleolus. However, the nucleolus integrity is not essential for both DOR nucleo-cytoplasmic shuttling and DOR function on basal autophagy. Taken together, we propose that DOR exit from the nucleus is essential for basal autophagy stimulation even under nucleolus disruption.
Bibliographical noteFunding Information:
We thank the Advanced Digital Microscopy Facility (IRB Barcelona), in particular Anna Lladó, Lidia Bardia and Carme Casals. Thanks also go to I. Castrillón, and J.C. Monasterio for technical assistance. We thank Ms. T. Yates for editorial support. We thank Dr. Neus Agell for kindly providing plasmids. C.M. and A.S. were respectively a FPI fellow and a FIS fellow (“Instituto de Salud Carlos III)”. This study was supported by research grants from the MEC (SAF2008-03803), Grant 2009SGR915 from the “Generalitat de Catalunya”, CIBERDEM (“Instituto de Salud Carlos III”), (INTERREG IV-B-SUDOE-FEDER (DIOMED, SOE1/P1/E178), and COST Action BM0602. A.Z. was the recipient of a Science Intensification Award from the University of Barcelona.
- Basal autophagy
- Nucleo-cytoplasmic shuttle