Interaction between the autophagy protein Beclin 1 and Na+,K+-ATPase during starvation, exercise, and ischemia

Álvaro F. Fernández, Yang Liu, Vanessa Ginet, Mingjun Shi, Jihoon Nah, Zhongju Zou, Anwu Zhou, Bruce A. Posner, Guanghua Xiao, Marion Tanguy, Valérie Paradis, Junichi Sadoshima, Pierre Emmanuel Rautou, Julien Puyal, Ming Chang Hu, Beth Levine

Research output: Contribution to journalArticle

Abstract

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 renal 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 hearts 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 crosstalk between cellular machinery that generates and consumes energy during stress may represent a fundamental homeostatic mechanism.

Original languageEnglish (US)
Article numbere133282
JournalJCI Insight
Volume5
Issue number1
DOIs
StatePublished - Jan 16 2020

ASJC Scopus subject areas

  • Medicine(all)

Fingerprint Dive into the research topics of 'Interaction between the autophagy protein Beclin 1 and Na<sup>+</sup>,K<sup>+</sup>-ATPase during starvation, exercise, and ischemia'. Together they form a unique fingerprint.

  • Cite this

    Fernández, Á. F., Liu, Y., Ginet, V., Shi, M., Nah, J., Zou, Z., Zhou, A., Posner, B. A., Xiao, G., Tanguy, M., Paradis, V., Sadoshima, J., Rautou, P. E., Puyal, J., Hu, M. C., & Levine, B. (2020). Interaction between the autophagy protein Beclin 1 and Na+,K+-ATPase during starvation, exercise, and ischemia. JCI Insight, 5(1), [e133282]. https://doi.org/10.1172/jci.insight.133282