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Regulation and Function of Autophagy During Ferroptosis

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Ferroptosis in Health and Disease

Abstract

Autophagy is an evolutionarily conserved catabolic process that allows lysosomes to degrade distinct cytoplasmic components, including unused proteins, damaged organelles, and invading pathogens. In many cases, an increase in autophagy will function as a programmed survival mechanism to protect against stress, injury, and infection. In some cases, excessive autophagy can act as a programmed cell death mechanism to initiate or mediate various types of regulated cell death. More recently, dysfunctional autophagy has been found to lead to excessive degradation of cytosolic components to trigger ferroptosis, an iron- and lipid peroxidation-dependent type of cell death. In particular, certain types of selective autophagy, such as ferritinophagy, lipophagy, clockophagy, and chaperone-mediated autophagy, contribute to iron accumulation and free radical damage during ferroptosis. Additionally, the autophagy core regulator BECN1 can promote ferroptosis through the control of the exchange of extracellular cystine and glutamate across the cellular plasma via binding to SLC7A11, a component of amino acid antiporter system xc −. Moreover, autophagy-mediated HMGB1 release is implicated in inflammation during ferroptotic cell death. These findings suggest that ferroptosis is a type of autophagy-dependent cell death. Here we summarize the mechanisms that regulate autophagy and how they may contribute to ferroptosis.

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Acknowledgments

We apologize to the researchers who were not referenced due to space limitations. We thank Dave Primm (Department of Surgery, University of Texas Southwestern Medical Center) for his critical reading of the manuscript.

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  1. Department of Surgery, UT Southwestern Medical Center, Dallas, TX, USA

    Daolin Tang & Rui Kang

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  1. Daolin Tang
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  2. Rui Kang
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Correspondence to Daolin Tang or Rui Kang .

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  1. Department of Surgery, UT Southwestern Medical Center, Dallas, TX, USA

    Daolin Tang

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Tang, D., Kang, R. (2019). Regulation and Function of Autophagy During Ferroptosis. In: Tang, D. (eds) Ferroptosis in Health and Disease. Springer, Cham. https://doi.org/10.1007/978-3-030-26780-3_3

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