Interaction between the autophagy protein Beclin 1 and Na+,K+-ATPase during starvation, exercise and ischemia
Creators
- 1. Center for Autophagy Research, Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, Texas, USA
- 2. Department of Fundamental Neurosciences, University of Lausanne, Lausanne, Switzerland and Clinic of Neonatology, Department of Women, Mother and Child, University Hospital Center of Vaud, Lausanne, Switzerland
- 3. Charles and Jane Pak Center for Mineral Metabolism and Clinical Research, University of Texas Southwestern Medical Center, Dallas, Texas, USA
- 4. Department of Cell Biology and Molecular Medicine, Cardiovascular Research Institute, Rutgers New Jersey Medical School, Newark, New Jersey, USA
- 5. Center for Autophagy Research, Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, Texas, USA and Howard Hughes Medical Institute
- 6. Department of Biochemistry, University of Texas Southwestern Medical Center, Dallas, Texas, USA.
- 7. Department of Clinical Sciences, University of Texas Southwestern Medical Center, Dallas, Texas, USA
- 8. Université de Paris, Centre de recherche sur l'inflammation, Inserm, Paris, France and Service d'Hépatologie, DHU Unity, Pôle des Maladies de l'Appareil Digestif, Hôpital Beaujon, AP-HP, Clichy, France
- 9. Université de Paris, Centre de recherche sur l'inflammation, Inserm, Paris, France and Service d'anatomie pathologique, Hôpital Beaujon, AP-HP, Clichy, France
- 10. Department of Fundamental Neurosciences, University of Lausanne, Lausanne, Switzerland
- 11. Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, Texas, USA and Charles and Jane Pak Center for Mineral Metabolism and Clinical Research, University of Texas Southwestern Medical Center, Dallas, Texas, USA
- 12. Center for Autophagy Research, and Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, Texas, USA and Howard Hughes Medical Institute
Description
Autosis is a distinct form of cell death that requires both autophagy genes and the Na+,K+-ATPase pump. However, the relationship between the autophagy machinery and Na+,K+-ATPase is unknown. We explored the hypothesis that Na+,K+-ATPase interacts with the autophagy protein Beclin 1 during stress and autosis-inducing conditions. Starvation increased the Beclin 1/Na+,K+-ATPase interaction in cultured cells, and this was blocked by cardiac glycosides, inhibitors of Na+,K+-ATPase. Increases in Beclin 1/Na+,K+-ATPase interaction were also observed in tissues from starved mice, livers of patients with anorexia nervosa, brains of neonatal rats subjected to cerebral hypoxia-ischemia (HI) and kidneys of mice subjected to renal ischemia reperfusion injury (IRI). Cardiac glycosides blocked the increased Beclin 1/Na+,K+-ATPase interaction during cerebral HI injury and renal IRI. In the mouse IRI model, cardiac glycosides reduced numbers of autotic cells in the kidney and improved clinical outcome. Moreover, blockade of endogenous cardiac glycosides increased Beclin 1/Na+,K+-ATPase interaction and autotic cell death in mouse heart during exercise. Thus, Beclin 1/Na+,K+-ATPase interaction is increased in stress conditions, and cardiac glycosides decrease this interaction and autosis in both pathophysiological and physiological settings. This cross-talk between cellular machinery that generates and consumes energy during stress may represent a fundamental homeostatic mechanism.
Files
Fernandez et al_JCI insight 2020.pdf
Files
(13.4 MB)
| Name | Size | Download all |
|---|---|---|
|
md5:38521499379914875b186c5742fbe283
|
13.4 MB | Preview Download |
Additional details
Related works
- Is published in
- Journal article: 10.1172/jci.insight.133282 (DOI)