Emerging roles for lipids in non-apoptotic cell death

Non-apoptotic regulated cell death (RCD) is essential to maintain organismal homeostasis and may be aberrantly activated during certain pathological states. Lipids are emerging as key components of several non-apoptotic RCD pathways. For example, a direct interaction between membrane phospholipids a...

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Bibliographic Details
Published in:Cell death and differentiation 2016-07, Vol.23 (7), p.1099-1109
Main Authors: Magtanong, L, Ko, P J, Dixon, S J
Format: Article
Language:English
Subjects:
Cell death
Cell Death - drug effects
Fatty Acids - metabolism
Glutathione Peroxidase - metabolism
Humans
Lipid Metabolism - physiology
Macrophages - cytology
Macrophages - drug effects
Macrophages - metabolism
Niemann-Pick Diseases - genetics
Niemann-Pick Diseases - metabolism
Niemann-Pick Diseases - pathology
Palmitic Acid - toxicity
Phospholipids - metabolism
Protein Kinases - metabolism
Review
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Summary:Non-apoptotic regulated cell death (RCD) is essential to maintain organismal homeostasis and may be aberrantly activated during certain pathological states. Lipids are emerging as key components of several non-apoptotic RCD pathways. For example, a direct interaction between membrane phospholipids and the pore-forming protein mixed lineage kinase domain-like (MLKL) is needed for the execution of necroptosis, while the oxidative destruction of membrane polyunsaturated fatty acids (PUFAs), following the inactivation of glutathione peroxidase 4 (GPX4), is a requisite gateway to ferroptosis. Here, we review the roles of lipids in the initiation and execution of these and other forms of non-apoptotic cell death. We also consider new technologies that are allowing for the roles of lipids and lipid metabolism in RCD to be probed in increasingly sophisticated ways. In certain cases, this new knowledge may enable the development of therapies that target lipids and lipid metabolic processes to enhance or suppress specific non-apoptotic RCD pathways.
ISSN:1350-9047
1476-5403
DOI:10.1038/cdd.2016.25