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Parisi et al manuscript and SI 2019.pdf (2.09 MB)
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Membrane Disruption by Very Long Chain Fatty Acids During Necroptosis

preprint
submitted on 02.05.2019 and posted on 06.05.2019 by Laura Parisi, Shahin Sowlati-Hashjin, Ilyas Berhane, Kevin Carter, Jonathan Lovell, Sherry Chemler, Mikko Karttunen, G. Ekin Atilla-Gokcumen
In this work we investigate the mechanisms by which very long chain fatty acids (VLCFA) contribute to membrane permeabilization during necroptosis, a form of highly regulated necrotic cell death. We show that inactivating fatty acid elongase ELOVL7 prevents VLCFA accumulation and necroptotic cell death, while it's overexpression causes membrane permeabilization. We show that VLCFA can directly permeabilize lipid bilayers and investigate the basis of these effects by molecular dynamics simulations. Finally, we show that VLCFA can be used as substrates for protein fatty acylation during necroptosis, suggesting another potential mechanism by which VLCFA may mediate membrane permeabilization.

Funding

NSF MCB1817468

NSF 1555220

NIH R01EB017270

NIH DP5OD017898

NIH GM078383

History

Email Address of Submitting Author

lrparisi@buffalo.edu

Institution

University at Buffalo, The State University of New York

Country

United States of America

ORCID For Submitting Author

0000-0003-4868-1426

Declaration of Conflict of Interest

The authors declare no competing financial interests.

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