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Cell Death via Lipid Peroxidation and Protein Aggregation Diseases

Department of Materials and Life Science, Faculty of Science and Technology, Seikei University, 3-3-1 Kichijojikitamachi, Musashino-shi, Tokyo 180-8633, Japan
Author to whom correspondence should be addressed.
Academic Editors: Edward B. Neufeld and Ann Graham
Biology 2021, 10(5), 399;
Received: 16 February 2021 / Revised: 13 April 2021 / Accepted: 29 April 2021 / Published: 4 May 2021
(This article belongs to the Special Issue Protein Folding, Aggregation, and Cell Death)
It is essential for cellular homeostasis that biomolecules, such as DNA, proteins, and lipids, function properly. Disturbance of redox homeostasis produces aberrant biomolecules, including oxidized lipids and misfolded proteins, which increase in cells. Aberrant biomolecules are removed by excellent cellular clearance systems. However, when excess aberrant biomolecules remain in the cell, they disrupt organelle and cellular functions, leading to cell death. These aberrant molecules aggregate and cause apoptotic and non-apoptotic cell death, leading to various protein aggregation diseases. Thus, we investigated the cell-death cross-linking between lipid peroxidation and protein aggregation.
Lipid peroxidation of cellular membranes is a complicated cellular event, and it is both the cause and result of various diseases, such as ischemia-reperfusion injury, neurodegenerative diseases, and atherosclerosis. Lipid peroxidation causes non-apoptotic cell death, which is associated with cell fate determination: survival or cell death. During the radical chain reaction of lipid peroxidation, various oxidized lipid products accumulate in cells, followed by organelle dysfunction and the induction of non-apoptotic cell death. Highly reactive oxidized products from unsaturated fatty acids are detected under pathological conditions. Pathological protein aggregation is the general cause of these diseases. The cellular response to misfolded proteins is well-known as the unfolded protein response (UPR) and it is partially concomitant with the response to lipid peroxidation. Moreover, the association between protein aggregation and non-apoptotic cell death by lipid peroxidation is attracting attention. The link between lipid peroxidation and protein aggregation is a matter of concern in biomedical fields. Here, we focus on lethal protein aggregation in non-apoptotic cell death via lipid peroxidation. We reviewed the roles of protein aggregation in the initiation and execution of non-apoptotic cell death. We also considered the relationship between protein aggregation and oxidized lipid production. We provide an overview of non-apoptotic cell death with a focus on lipid peroxidation for therapeutic targeting during protein aggregation diseases. View Full-Text
Keywords: lipid peroxidation; cell signaling; protein aggregation; non-apoptotic cell death lipid peroxidation; cell signaling; protein aggregation; non-apoptotic cell death
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MDPI and ACS Style

Iuchi, K.; Takai, T.; Hisatomi, H. Cell Death via Lipid Peroxidation and Protein Aggregation Diseases. Biology 2021, 10, 399.

AMA Style

Iuchi K, Takai T, Hisatomi H. Cell Death via Lipid Peroxidation and Protein Aggregation Diseases. Biology. 2021; 10(5):399.

Chicago/Turabian Style

Iuchi, Katsuya, Tomoka Takai, and Hisashi Hisatomi. 2021. "Cell Death via Lipid Peroxidation and Protein Aggregation Diseases" Biology 10, no. 5: 399.

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