Abstract
Purpose of Review
Autophagy is a conserved intracellular degradation system and plays a dual role in cell death, depending on context and phase. Ferroptosis is a new form of regulated cell death that mainly depends on iron accumulation and lipid peroxidation. In this review, we summarize the processes of autophagy and ferroptosis and discuss their crosstalk mechanisms at the molecular level.
Recent Findings
The original study shows that ferroptosis is morphologically, biochemically, and genetically distinct from autophagy and other types of cell death. However, recent studies demonstrate that activation of ferroptosis is indeed dependent on the induction of autophagy. Additionally, many ferroptosis regulators such as SLC7A11, GPX4, NRF2, p53, HSPB1, CISD1, FANCD2, and ACSL4 have been identified as potential regulators of autophagy.
Summary
This review not only highlights the importance of autophagy as an emerging mechanism of ferroptosis but also raises new insights regarding regulated cell death.
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Abbreviations
- RCD:
-
Regulated cell death
- ATG:
-
Autophagy-regulated
- TEM:
-
Transmission electron microscopy
- RSL:
-
RAS-selective lethal
- RIPK:
-
Receptor interacting serine/threonine kinase
- ROS:
-
Reactive oxygen species
- NCOA4:
-
Nuclear receptor coactivator 4
- GSH:
-
Glutathione
- SLC7A11:
-
Solute carrier family 7 member 11
- GPX:
-
Glutathione peroxidase
- SAT1:
-
Spermidine/spermine N1-acetyltransferase 1
- GLS2:
-
Glutaminase 2
- NRF2:
-
Nuclear factor erythroid 2-related factor 2
- KEAP1:
-
Kelch-like ECH-associated protein 1
- HSPB1:
-
Heat shock protein family B (small) member 1
- CISD1:
-
CDGSH iron sulfur domain 1
- FA:
-
Fanconi anemia
- ACSL4:
-
Acyl-CoA synthetase long-chain family member 4
- mTOR:
-
Mechanistic target of rapamycin
- FTH:
-
Ferritin heavy chain
- FTL:
-
Ferritin light chain
- BMSCs:
-
Bone marrow stromal cells
- HSPA5:
-
The heat shock 70 kDa protein 5
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Acknowledgments
We thank Christine Heiner (Department of Surgery, University of Pittsburgh) for her critical reading of the manuscript. This work was supported by the National Institutes of Health of the USA (R01GM115366 and R01CA160417), the National Natural Science Foundation of China (31671435), the National Natural Science Foundation of Guangdong (2016A030308.), and a Research Scholar Grant from the American Cancer Society (RSG-16-014-01-CDD).
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Rui Kang and Daolin Tang declare that they have no conflicts of interest.
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Kang, R., Tang, D. Autophagy and Ferroptosis—What Is the Connection?. Curr Pathobiol Rep 5, 153–159 (2017). https://doi.org/10.1007/s40139-017-0139-5
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DOI: https://doi.org/10.1007/s40139-017-0139-5