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

Publisher: American Society for Clinical Investigation Country of Publication: United States NLM ID: 101676073 Publication Model: Electronic Cited Medium: Internet ISSN: 2379-3708 (Electronic) Linking ISSN: 23793708 NLM ISO Abbreviation: JCI Insight Subsets: MEDLINE

Original Publication: Ann Arbor, Michigan : American Society for Clinical Investigation, [2016]-

Autophagy/*physiology ; Beclin-1/*metabolism ; Ischemia/*metabolism ; Sodium-Potassium-Exchanging ATPase/*metabolism ; Starvation/*metabolism; Animals ; Cell Death/physiology ; Cells, Cultured ; Glycosides ; HeLa Cells ; Humans ; Male ; Mice ; Mice, Inbred C57BL ; Rats ; Rats, Sprague-Dawley ; Reperfusion Injury

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.

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U19 AI109725 United States AI NIAID NIH HHS; R01 HL091469 United States HL NHLBI NIH HHS; R01 DK091392 United States DK NIDDK NIH HHS; S10 OD021684 United States OD NIH HHS; R01 HL112330 United States HL NHLBI NIH HHS; U19 AI142784 United States AI NIAID NIH HHS; R01 CA109618 United States CA NCI NIH HHS; R01 DK092461 United States DK NIDDK NIH HHS; R01 HL138720 United States HL NHLBI NIH HHS

Keywords: Autophagy; Cell Biology; Cell stress

0 (Beclin-1)
0 (Glycosides)
EC 7.2.2.13 (Sodium-Potassium-Exchanging ATPase)

Date Created: 20200117 Date Completed: 20210510 Latest Revision: 20210606

20240513

PMC7030824

10.1172/jci.insight.133282

31941841