ROS, Stress and Regeneration

December 12th 2018
Versione stampabile

Venue: Edificio Povo 2, via Sommarive nr. 9, Povo (Tn) - Room B102


Time: 12.15 p.m.


Speaker:

Serras Rigalt Florencio - University of Barcelona


Oxidative stress initiated by dying or damaged cells propagates to neighboring undamaged cells, activating the MAP kinases JNK and p38 for cytokine-dependent regenerative growth. However, the stress sensing mechanism by which neighboring undamaged cells trigger this activation is unknown. The Apoptosis Signal-regulating Kinase 1 (ASK1), a serine/threonine kinase belonging to the MAPKKK family acts as an intracellular sensor that responds to various stresses by phosphorylation of the JNK and p38 MAK pathways during Drosophila imaginal disc regeneration. We investigate regeneration by conditionally inducing cell death in specific domains of the wing imaginal disc of Drosophila, under different genetic backgrounds. We have found that Drosophila Ask1 senses reactive oxygen species (ROS) differently in damaged and undamaged cells and is required for regeneration. Stressed apoptotic cells produce high levels of ROS and promote high Ask1 activity. Neighboring undamaged cells shown low levels of ROS and activate Ask1, but such activity is attenuated by Pi3K dependent Akt1 phosphorylation. This attenuated activity of Ask1 in undamaged cells is necessary to drive regeneration. In conclusion, we have demonstrated that the oxidative stress produced by ROS in apoptotic cells is sensed in neighboring cells by Ask1 and Akt1. This indicates that ROS act as a true signaling mechanism for regeneration. These findings contribute to our understanding of the molecular mechanism of communication between dying and living cells to trigger regeneration.