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Exogenous Monounsaturated Fatty Acids Suppress Non-Apoptotic Cell Death

65 Pages Posted: 7 Jun 2018 Sneak Peek Status: Review Complete

See all articles by Leslie Magtanong

Leslie Magtanong

Stanford University - Department of Biology

Pin-Joe Ko

Stanford University - Department of Biology

Milton To

University of California, Berkeley - Department of Nutritional Sciences and Toxicology

Jennifer Y. Cao

Stanford University - Department of Biology

Amy N. Tarangelo

Stanford University - Department of Biology

Carl C. Ward

University of California, Berkeley - Department of Chemistry

Kevin Y. Cho

University of Washington - Department of Medicine

Gary J. Patti

University of Washington - Department of Medicine

Daniel K. Nomura

University of California, Berkeley - Department of Nutritional Sciences and Toxicology

James A. Olzmann

University of California, Berkeley - Department of Nutritional Sciences and Toxicology

Scott J. Dixon

Stanford University - Department of Biology

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Abstract

The initiation and execution of cell death is regulated by various lipids. How the levels of environmental (exogenous) lipids impact cell death sensitivity is not well understood. Using a high-throughput lipid modulation screen we find that physiological levels of extracellular free fatty acids have diverse effects on non-apoptotic and apoptotic cell death induced by lethal small molecules and natural products. In particular, monounsaturated fatty acids (MUFAs) are found to suppress the non-apoptotic, iron-dependent cell death process of ferroptosis. This protective effect requires acyl-CoA synthetase long-chain family member 3 (ACSL3) and involves suppression of toxic lipid ROS accumulation specifically at the plasma membrane. Exogenous MUFAs also protect cells from apoptotic lipotoxicity caused by the accumulation of saturated fatty acids, but through a genetically distinct mechanism. Thus, MUFAs emerge as key lipid metabolites regulating both non-apoptotic and apoptotic cell death.

Suggested Citation

Magtanong, Leslie and Ko, Pin-Joe and To, Milton and Cao, Jennifer Y. and Tarangelo, Amy N. and Ward, Carl C. and Cho, Kevin Y. and Patti, Gary J. and Nomura, Daniel K. and Olzmann, James A. and Dixon, Scott J., Exogenous Monounsaturated Fatty Acids Suppress Non-Apoptotic Cell Death (2018). Available at SSRN: https://ssrn.com/abstract=3188426 or http://dx.doi.org/10.2139/ssrn.3188426
This is a paper under consideration at Cell Press and has not been peer-reviewed.

Leslie Magtanong

Stanford University - Department of Biology

Gilbert Building, Rm 109
371 Serra Mall
Stanford, CA 94305
United States

Pin-Joe Ko

Stanford University - Department of Biology

Gilbert Building, Rm 109
371 Serra Mall
Stanford, CA 94305
United States

Milton To

University of California, Berkeley - Department of Nutritional Sciences and Toxicology

Berkeley, CA
United States

Jennifer Y. Cao

Stanford University - Department of Biology

Gilbert Building, Rm 109
371 Serra Mall
Stanford, CA 94305
United States

Amy N. Tarangelo

Stanford University - Department of Biology

Gilbert Building, Rm 109
371 Serra Mall
Stanford, CA 94305
United States

Carl C. Ward

University of California, Berkeley - Department of Chemistry

310 Barrows Hall
Berkeley, CA 94720
United States

Kevin Y. Cho

University of Washington - Department of Medicine

Box 356340
1925 N.E. Pacific Street
Seattle, WA 98195-6340
United States

Gary J. Patti

University of Washington - Department of Medicine

Box 356340
1925 N.E. Pacific Street
Seattle, WA 98195-6340
United States

Daniel K. Nomura

University of California, Berkeley - Department of Nutritional Sciences and Toxicology

Berkeley, CA
United States

James A. Olzmann

University of California, Berkeley - Department of Nutritional Sciences and Toxicology

Berkeley, CA
United States

Scott J. Dixon (Contact Author)

Stanford University - Department of Biology ( email )

Gilbert Building, Rm 109
371 Serra Mall
Stanford, CA 94305
United States