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Autophagy and Ferroptosis—What Is the Connection?

  • Autophagy in Pathobiology (W-X Ding and H-M Shen, Section Editors)
  • Published:
Current Pathobiology Reports

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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Correspondence to Daolin Tang.

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Rui Kang and Daolin Tang declare that they have no conflicts of interest.

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This article is part of the Topical Collection on Autophagy in Pathobiology

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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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