BECN1 is a new driver of ferroptosis

Rui Kang, Shan Zhu, Herbert J. Zeh, Daniel J. Klionsky, Daolin Tang

Research output: Contribution to journalComment/debate

9 Citations (Scopus)

Abstract

Ferroptosis is a form of regulated cell death caused by iron accumulation and oxidative injury. BECN1 is a key regulator of macroautophagy/autophagy, a catabolic process of degradation induced by starvation or other stressors. Our recent findings reveal a novel alternative mechanism by which BECN1 can promote ferroptosis through the regulation of activity of the cysteine and glutamate antiporter system xc in cancer cells. BECN1-dependent autophagy requires the formation of the BECN1-containing class III phosphatidylinositol 3-kinase (PtdIns3K) complex, whereas BECN1-dependent ferroptosis requires the formation of a BECN1-SLC7A11 complex. Furthermore, AMP-activated protein kinase (AMPK) is required for BECN1 phosphorylation to trigger formation of the BECN1-SLC7A11 complex in the process of inhibiting system xc activity and inducing lipid peroxidation. These findings suggest that the autophagy-dependent and -independent functions of BECN1 play distinct roles in regulated cell death.

Original languageEnglish (US)
Pages (from-to)2173-2175
Number of pages3
JournalAutophagy
Volume14
Issue number12
DOIs
StatePublished - Dec 2 2018

Fingerprint

Autophagy
Class III Phosphatidylinositol 3-Kinases
Cell Death
Antiporters
AMP-Activated Protein Kinases
Starvation
Lipid Peroxidation
Cysteine
Glutamic Acid
Iron
Phosphorylation
Wounds and Injuries
Neoplasms

Keywords

  • AMPK
  • autophagy
  • BECN1
  • cancer
  • chemotherapy
  • ferroptosis
  • phosphorylation
  • redox
  • SLC7A11

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

Cite this

BECN1 is a new driver of ferroptosis. / Kang, Rui; Zhu, Shan; Zeh, Herbert J.; Klionsky, Daniel J.; Tang, Daolin.

In: Autophagy, Vol. 14, No. 12, 02.12.2018, p. 2173-2175.

Research output: Contribution to journalComment/debate

Kang, Rui ; Zhu, Shan ; Zeh, Herbert J. ; Klionsky, Daniel J. ; Tang, Daolin. / BECN1 is a new driver of ferroptosis. In: Autophagy. 2018 ; Vol. 14, No. 12. pp. 2173-2175.
@article{f048b77cbcc443a3a7c0c7971d187c16,
title = "BECN1 is a new driver of ferroptosis",
abstract = "Ferroptosis is a form of regulated cell death caused by iron accumulation and oxidative injury. BECN1 is a key regulator of macroautophagy/autophagy, a catabolic process of degradation induced by starvation or other stressors. Our recent findings reveal a novel alternative mechanism by which BECN1 can promote ferroptosis through the regulation of activity of the cysteine and glutamate antiporter system xc − in cancer cells. BECN1-dependent autophagy requires the formation of the BECN1-containing class III phosphatidylinositol 3-kinase (PtdIns3K) complex, whereas BECN1-dependent ferroptosis requires the formation of a BECN1-SLC7A11 complex. Furthermore, AMP-activated protein kinase (AMPK) is required for BECN1 phosphorylation to trigger formation of the BECN1-SLC7A11 complex in the process of inhibiting system xc − activity and inducing lipid peroxidation. These findings suggest that the autophagy-dependent and -independent functions of BECN1 play distinct roles in regulated cell death.",
keywords = "AMPK, autophagy, BECN1, cancer, chemotherapy, ferroptosis, phosphorylation, redox, SLC7A11",
author = "Rui Kang and Shan Zhu and Zeh, {Herbert J.} and Klionsky, {Daniel J.} and Daolin Tang",
year = "2018",
month = "12",
day = "2",
doi = "10.1080/15548627.2018.1513758",
language = "English (US)",
volume = "14",
pages = "2173--2175",
journal = "Autophagy",
issn = "1554-8627",
publisher = "Landes Bioscience",
number = "12",

}

TY - JOUR

T1 - BECN1 is a new driver of ferroptosis

AU - Kang, Rui

AU - Zhu, Shan

AU - Zeh, Herbert J.

AU - Klionsky, Daniel J.

AU - Tang, Daolin

PY - 2018/12/2

Y1 - 2018/12/2

N2 - Ferroptosis is a form of regulated cell death caused by iron accumulation and oxidative injury. BECN1 is a key regulator of macroautophagy/autophagy, a catabolic process of degradation induced by starvation or other stressors. Our recent findings reveal a novel alternative mechanism by which BECN1 can promote ferroptosis through the regulation of activity of the cysteine and glutamate antiporter system xc − in cancer cells. BECN1-dependent autophagy requires the formation of the BECN1-containing class III phosphatidylinositol 3-kinase (PtdIns3K) complex, whereas BECN1-dependent ferroptosis requires the formation of a BECN1-SLC7A11 complex. Furthermore, AMP-activated protein kinase (AMPK) is required for BECN1 phosphorylation to trigger formation of the BECN1-SLC7A11 complex in the process of inhibiting system xc − activity and inducing lipid peroxidation. These findings suggest that the autophagy-dependent and -independent functions of BECN1 play distinct roles in regulated cell death.

AB - Ferroptosis is a form of regulated cell death caused by iron accumulation and oxidative injury. BECN1 is a key regulator of macroautophagy/autophagy, a catabolic process of degradation induced by starvation or other stressors. Our recent findings reveal a novel alternative mechanism by which BECN1 can promote ferroptosis through the regulation of activity of the cysteine and glutamate antiporter system xc − in cancer cells. BECN1-dependent autophagy requires the formation of the BECN1-containing class III phosphatidylinositol 3-kinase (PtdIns3K) complex, whereas BECN1-dependent ferroptosis requires the formation of a BECN1-SLC7A11 complex. Furthermore, AMP-activated protein kinase (AMPK) is required for BECN1 phosphorylation to trigger formation of the BECN1-SLC7A11 complex in the process of inhibiting system xc − activity and inducing lipid peroxidation. These findings suggest that the autophagy-dependent and -independent functions of BECN1 play distinct roles in regulated cell death.

KW - AMPK

KW - autophagy

KW - BECN1

KW - cancer

KW - chemotherapy

KW - ferroptosis

KW - phosphorylation

KW - redox

KW - SLC7A11

UR - http://www.scopus.com/inward/record.url?scp=85053322934&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85053322934&partnerID=8YFLogxK

U2 - 10.1080/15548627.2018.1513758

DO - 10.1080/15548627.2018.1513758

M3 - Comment/debate

C2 - 30145930

AN - SCOPUS:85053322934

VL - 14

SP - 2173

EP - 2175

JO - Autophagy

JF - Autophagy

SN - 1554-8627

IS - 12

ER -