Autophagy compensates for Lkb1 loss to maintain adult mice homeostasis and survival
- Rutegrs Cancer Institute of New Jersey, United States
- Rutgers Cancer Institute of New Jersey, United States
Abstract
Liver Kinase B1 (LKB1), also known as serine/threonine kinase 11 (STK11) is the major energy sensor for cells to respond to metabolic stress. Autophagy degrades and recycles proteins, macromolecules, and organelles for cells to survive starvation. To access the role and cross-talk between autophagy and Lkb1 in normal tissue homeostasis, we generated genetically engineered mouse models where we can conditionally delete Stk11 and autophagy essential gene, Atg7, respectively or simultaneously, throughout the adult mice. We found that Lkb1 was essential for the survival of adult mice, and autophagy activation could temporarily compensate for the acute loss of Lkb1 and extend mouse life span. We further found that acute deletion of Lkb1 in adult mice led to impaired intestinal barrier function, hypoglycemia, and abnormal serum metabolism, which was partly rescued by the Lkb1 loss-induced autophagy upregulation via inhibiting p53 induction. Taken together, we demonstrated that autophagy and Lkb1 work synergistically to maintain adult mouse homeostasis and survival.
Data availability
All data generated or analysed during this study are included in the manuscript and supporting files.
Article and author information
Author details
Jessie Yanxiang Guo
Funding
National Cancer Institute (R01CA237347-01A1)
- Jessie Yanxiang Guo
Mistletoe Research Fellowship (Predoctoral fellowship)
- Vrushank Bhatt
National Cancer Institute (K22 CA190521)
- Jessie Yanxiang Guo
American Cancer Society (134036-RSG-19-165-01-TBG)
- Jessie Yanxiang Guo
GO2 Foundation for Lung Cancer (Young Innovators Team Awards)
- Jessie Yanxiang Guo
Lung Cancer Research Foundation (Research Grant)
- Jessie Yanxiang Guo
New Jersey Commission on Cancer Research (DFHS18PPC021,Postdoc fellowship)
- Khoosheh Khayati
New Jersey Commission on Cancer Research (DCHS19PPC013,Predoctoral fellowship)
- Vrushank Bhatt
Rutgers Busch Biomedical grant (Research Grant)
- Jessie Yanxiang Guo
Cox Foundation for Cancer Research (Predoctoral fellowship)
- Vrushank Bhatt
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Ethics
Animal experimentation: This study was performed in strict accordance with the recommendations in the Guide for the Care and Use of Laboratory Animals of the National Institutes of Health. All of the animals were handled according to approved institutional animal care and use committee (IACUC) protocols (#I15-074) of the Rutgers University.
Copyright
© 2020, Khayati et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Autophagy compensates for Lkb1 loss to maintain adult mice homeostasis and survival
eLife 9:e62377.
https://doi.org/10.7554/eLife.62377
