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Autophagy-Dependent Ferroptosis in Cancer.
- Source :
-
Antioxidants & redox signaling [Antioxid Redox Signal] 2023 Jul; Vol. 39 (1-3), pp. 79-101. Date of Electronic Publication: 2023 Mar 09. - Publication Year :
- 2023
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Abstract
- Significance: Autophagy is a self-degrading process that determines cell fate in response to various environmental stresses. In contrast to autophagy-mediated cell survival, the signals, mechanisms, and effects of autophagy-dependent cell death remain obscure. The discovery of autophagy-dependent ferroptosis provides a paradigm for understanding the relationship between aberrant degradation pathways and excessive lipid peroxidation in driving regulated cell death. Recent Advances: Ferroptosis was originally described as an autophagy-independent and iron-mediated nonapoptotic cell death. Current studies reveal that the level of intracellular autophagy is positively correlated with ferroptosis sensitivity. Selective autophagic degradation of proteins ( e.g. , ferritin, SLC40A1, ARNTL, GPX4, and CDH2) or organelles ( e.g. , lipid droplets or mitochondria) promotes ferroptosis by inducing iron overload and/or lipid peroxidation. Several upstream autophagosome regulators ( e.g. , TMEM164), downstream autophagy receptors ( e.g. , HPCAL1), or danger signals ( e.g. , DCN) are selectively required for ferroptosis-related autophagy, but not for starvation-induced autophagy. The induction of autophagy-dependent ferroptosis is an effective approach to eliminate drug-resistant cancer cells. Critical Issues: How different organelles selectively activate autophagy to modulate ferroptosis sensitivity is not fully understood. Identifying direct protein effectors of ferroptotic cell death remains a challenge. Future Directions: Further understanding of the molecular mechanics and immune consequences of autophagy-dependent ferroptosis is critical for the development of precision antitumor therapies. Antioxid. Redox Signal . 39, 79-101.
- Subjects :
- Humans
Cell Death
Iron metabolism
Autophagy
Ferroptosis
Neoplasms
Subjects
Details
- Language :
- English
- ISSN :
- 1557-7716
- Volume :
- 39
- Issue :
- 1-3
- Database :
- MEDLINE
- Journal :
- Antioxidants & redox signaling
- Publication Type :
- Academic Journal
- Accession number :
- 36734418
- Full Text :
- https://doi.org/10.1089/ars.2022.0202