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Heat Shock Proteins: Endogenous Modulators of Ferroptosis

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Book cover Ferroptosis in Health and Disease

Abstract

The heat shock response is a transcriptional reprogramming mechanism used by cells to prevent damage or death. This highly conserved process is often involved in the upregulation of heat shock proteins (HSPs) by the activation of heat shock factors in response to external or internal stresses. Based on their molecular size, HSPs can be classified into six subfamilies, namely, HSP100, HSP90, HSP70, HSP60, HSP40, and small heat shock proteins. These HSPs play multiple roles in protein homeostasis, including the folding, unfolding, assembly, transport, sorting, or degradation of proteins. A dynamic HSP family network has long been implicated in the regulation of oxidative stress and regulated cell death. Ferroptosis is an iron- and lipid peroxidation-dependent type of necrosis that is implicated in tissue injury and cancer therapy. Unlike their role in mediating apoptosis resistance, HSPs play a dual role in ferroptosis, according to recent studies. In particular, inducible HSPB1 (also known as HSP25 in mouse or HSP27 in human)-dependent actin dynamics as well as inducible HSPA5 (also known as BIP or GRP78)-mediated GPX4 protein stability inhibits ferroptosis via blocking iron uptake and lipid peroxidation, respectively. In contrast, constitutively HSP90-related LAMP2A protein stability promotes GPX4 degradation and subsequent ferroptosis via the upregulation of HSPA8 (also known as HSC70)-mediated autophagy. In this chapter, we summarize the classification and function of HSPs and discuss the regulation of ferroptosis by HSPs.

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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

    Rui Kang & Daolin Tang

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

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

    Daolin Tang

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Kang, R., Tang, D. (2019). Heat Shock Proteins: Endogenous Modulators of Ferroptosis. In: Tang, D. (eds) Ferroptosis in Health and Disease. Springer, Cham. https://doi.org/10.1007/978-3-030-26780-3_4

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