Energy-stress-mediated AMPK Activation Inhibits Ferroptosis

Overview

Journal Nat Cell Biol

Specialty Cell Biology

Date 2020 Feb 8

PMID 32029897

Citations 455

Authors

Hyemin Lee

Fereshteh Zandkarimi

Yilei Zhang

Jitendra Kumar Meena

Jongchan Kim

Li Zhuang

Siddhartha Tyagi

Li Ma

Thomas F Westbrook

Gregory R Steinberg

Daisuke Nakada

Brent R Stockwell

Boyi Gan

Affiliations

Soon will be listed here.

Abstract

Energy stress depletes ATP and induces cell death. Here we identify an unexpected inhibitory role of energy stress on ferroptosis, a form of regulated cell death induced by iron-dependent lipid peroxidation. We found that ferroptotic cell death and lipid peroxidation can be inhibited by treatments that induce or mimic energy stress. Inactivation of AMP-activated protein kinase (AMPK), a sensor of cellular energy status, largely abolishes the protective effects of energy stress on ferroptosis in vitro and on ferroptosis-associated renal ischaemia-reperfusion injury in vivo. Cancer cells with high basal AMPK activation are resistant to ferroptosis and AMPK inactivation sensitizes these cells to ferroptosis. Functional and lipidomic analyses further link AMPK regulation of ferroptosis to AMPK-mediated phosphorylation of acetyl-CoA carboxylase and polyunsaturated fatty acid biosynthesis. Our study demonstrates that energy stress inhibits ferroptosis partly through AMPK and reveals an unexpected coupling between ferroptosis and AMPK-mediated energy-stress signalling.

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