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Cited by 16Mitochondrial Function and PathologyRedox biology and oxidative stressAutophagy in Disease and Therapy

ROS signaling–induced mitochondrial Sgk1 expression regulates epithelial cell renewal

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Li, Yingxiang, Liu, Chengdong, Rolling, Luke, Sikora, Veronica, Chen, Zhimin, Gurwin, Jack, Barabell, Caroline, Lin, Jiandie +1 more·2023·Proceedings of the National Academy of Sciences
DOI 10.1073/pnas.2216310120PMC PMC10268254
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Abstract

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.

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Cited by

Sorted by citations

Authors
Li, Y., Liu, C., Rolling, L., Sikora, V., Chen, Z., Gurwin, J., Barabell, C., Lin, J., & Duan, C.
Affiliations
University of Michigan (US)
Corresponding author
Duan, Cunming
ORCID
Venue
Proceedings of the National Academy of Sciences
Publisher
National Academy of Sciences
Published
2023-06-05
Volume
120
Issue
24
Pages
e2216310120-e2216310120
ISSN
  • 0027-8424 (ISSN-L)
  • 1091-6490
DOI
10.1073/pnas.2216310120
PMC
PMC10268254
OpenAlex
W4379468999
Cited by
16
References
2
Citations by year
2026: 6 · 2025: 4 · 2024: 4 · 2023: 2
FWCI
1.42
Type
journal article
Language
en
Open access
Licence
Locations
  • Proceedings of the National Academy of Sciences (publishedVersion, cc-by-nc-nd)
  • PubMed Central (publishedVersion, cc-by-nc-nd)
  • PubMed (publishedVersion)
Funders
Center for Hierarchical Manufacturing, National Science Foundation (IOS-1755268, IOS-1557850)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Redox biology and oxidative stress
  • Health Sciences › Medicine › Epidemiology › Autophagy in Disease and Therapy
Keywords
SGK1, mitochondrial reactive oxygen species, cell cycle re-entry, mitochondrial metabolism, ATP synthase, mitochondrial membrane potential, epithelial cell renewal, zebrafish, breast cancer cells
MeSH terms
Adenosine Triphosphate, Animals, Epithelial Cells, Humans, Mitochondria, Zebrafish, Reactive Oxygen Species

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