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 language | English (US) |
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Pages (from-to) | 2173-2175 |
Number of pages | 3 |
Journal | Autophagy |
Volume | 14 |
Issue number | 12 |
DOIs |
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State | Published - Dec 2 2018 |
Keywords
- AMPK
- BECN1
- SLC7A11
- autophagy
- cancer
- chemotherapy
- ferroptosis
- phosphorylation
- redox
ASJC Scopus subject areas
- Molecular Biology
- Cell Biology