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Lipoxygenase in Ferroptosis

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Ferroptosis in Health and Disease

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Abstract

Cell death is indispensable for the maintenance of organic homeostasis and embryonic development under physical circumstances. Ferroptosis is a newly discovered type of cell death by Stockwell research group in 2012. It is distinct from other cell death modalities including apoptosis, necroptosis, autophagy, and pyroptosis at morphological, genetic, and biochemical levels. It is well known that ferroptotic cell death occurs through lipid peroxidation accumulation. Lipoxygenase (ALOX) serves as one of the major enzymes for the oxygenation of arachidonic acid (AA), an essential polyunsaturated fatty acid (PUFA), finally triggering lipid peroxidation and ferroptosis. Here, we make a summarization of basic knowledge of ALOX including its nomenclature, distribution in different organs, and its metabolites. Additionally, the relationship between ALOX and ferroptosis in human diseases such as neurological disorders and cancers is also discussed. We propose that ALOX may serve as a potential therapeutic target for treating multiple disorders via suppressing ferroptosis.

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Abbreviations

AA:

Arachidonic acid

ACSL4:

Acyl-CoA synthetase long chain family member 4

AD:

Alzheimer’s disease

AdA:

Adrenic acid

ALOX:

Lipoxygenase

DHA:

Docosahexaenoic acid

EPA:

Eicosapentaenoic acid

Fer-1:

Ferrostatin-1

GPX4:

Glutathione peroxidase 4

HETE:

Hydroxyeicosatetraenoic acid

HPETE:

Hydroperoxyeicosatetraenoic acid

HPODE:

Hydroperoxyoctadecadienoic acid

HODE:

Hydroxyoctadecadienoic acid

LA:

Linoleic acid

LT:

Leukotriene

PE:

Phosphatidylethanolamine

PEBP1:

PE-binding protein 1

PUFAs:

Polyunsaturated fatty acids

ROS:

Reactive oxygen species

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Authors and Affiliations

  1. Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha, P. R. China

    Xiaoyuan Mao

  2. Hunan Key Laboratory of Pharmacogenetics, Institute of Clinical Pharmacology, Central South University, Changsha, P. R. China

    Xiaoyuan Mao

  3. Engineering Research Center of Applied Technology of Pharmacogenomics, Ministry of Education, Changsha, P. R. China

    Xiaoyuan Mao

  4. National Clinical Research Center for Geriatric Disorders, Changsha, Hunan, P. R. China

    Xiaoyuan Mao

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  1. Xiaoyuan Mao
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Editors and Affiliations

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

    Daolin Tang

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Mao, X. (2019). Lipoxygenase in Ferroptosis. In: Tang, D. (eds) Ferroptosis in Health and Disease. Springer, Cham. https://doi.org/10.1007/978-3-030-26780-3_16

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