Journal
AUTOPHAGY
Volume 14, Issue 12, Pages 2173-2175Publisher
TAYLOR & FRANCIS INC
DOI: 10.1080/15548627.2018.1513758
Keywords
AMPK; autophagy; BECN1; cancer; chemotherapy; ferroptosis; phosphorylation; redox; SLC7A11
Categories
Funding
- National Institutes of Health [R01GM115366, R01CA160417, R01CA211070, R01GM127791, R01GM053396]
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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 x(c)(-) 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 x(c)(-) activity and inducing lipid peroxidation. These findings suggest that the autophagy-dependent and -independent functions of BECN1 play distinct roles in regulated cell death.
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