title: Emerging roles for lipids in non-apoptotic cell death.
abstract: 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.
authors.affiliation: Department of Biology, Stanford University, 337 Campus Drive, Stanford, CA, USA.
authors.forename: L
authors.initials: L
authors.lastname: Magtanong
authors.affiliation: Department of Biology, Stanford University, 337 Campus Drive, Stanford, CA, USA.
authors.forename: P J
authors.initials: PJ
authors.lastname: Ko
authors.affiliation: Department of Biology, Stanford University, 337 Campus Drive, Stanford, CA, USA.
authors.forename: S J
authors.initials: SJ
authors.lastname: Dixon
mesh_terms: D016923:Cell Death / Q000187:drug effects; D005227:Fatty Acids / Q000378:metabolism; D005979:Glutathione Peroxidase / Q000378:metabolism; D006801:Humans; D050356:Lipid Metabolism / Q000502:physiology*; D008264:Macrophages / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D009542:Niemann-Pick Diseases / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D019308:Palmitic Acid / Q000633:toxicity; D000080662:Phospholipid Hydroperoxide Glutathione Peroxidase; D010743:Phospholipids / Q000378:metabolism; D011494:Protein Kinases / Q000378:metabolism
chemical_list: D005227:Fatty Acids; D010743:Phospholipids; D019308:Palmitic Acid; D000080662:Phospholipid Hydroperoxide Glutathione Peroxidase; D005979:Glutathione Peroxidase; C570693:MLKL protein, human; D011494:Protein Kinases