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Title: ROS signaling–induced mitochondrial Sgk1 expression regulates epithelial cell renewal
Many types of differentiated cells can reenter the cell cycle upon injury or stress. The underlying mechanisms are still poorly understood. Here, we investigated how quiescent cells are reactivated using a zebrafish model, in which a population of differentiated epithelial cells are reactivated under a physiological context. A robust and sustained increase in mitochondrial membrane potential was observed in the reactivated cells. Genetic and pharmacological perturbations show that elevated mitochondrial metabolism and ATP synthesis are critical for cell reactivation. Further analyses showed that elevated mitochondrial metabolism increases mitochondrial ROS levels, which induces Sgk1 expression in the mitochondria. Genetic deletion and inhibition of Sgk1 in zebrafish abolished epithelial cell reactivation. Similarly, ROS-dependent mitochondrial expression of SGK1 promotes S phase entry in human breast cancer cells. Mechanistically, SGK1 coordinates mitochondrial activity with ATP synthesis by phosphorylating F 1 F o -ATP synthase. These findings suggest a conserved intramitochondrial signaling loop regulating epithelial cell renewal.  more » « less
Award ID(s):
1755268
PAR ID:
10437057
Author(s) / Creator(s):
; ; ; ; ; ; ; ;
Date Published:
Journal Name:
Proceedings of the National Academy of Sciences
Volume:
120
Issue:
24
ISSN:
0027-8424
Format(s):
Medium: X
Sponsoring Org:
National Science Foundation
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