A novel role for 12/15-lipoxygenase in regulating autophagy

Morgan, Alwena H., Hammond, Victoria J., Sakoh-Nakatogawa, Machiko, Ohsumi, Yoshinori, Thomas, Christopher P. ORCID: https://orcid.org/0000-0001-5840-8613, Blanchet, Fabien, Piguet, Vincent, Kiselyov, Kirill and O'Donnell, Valerie Bridget ORCID: https://orcid.org/0000-0003-4089-8460 2015. A novel role for 12/15-lipoxygenase in regulating autophagy. Redox Biology 4 , pp. 40-47. 10.1016/j.redox.2014.11.005

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Abstract

12/15-Lipoxygenase (LOX) enzymatically generates oxidized phospholipids in monocytes and macrophages. Herein, we show that cells deficient in 12/15-LOX contain defective mitochondria and numerous cytoplasmic vacuoles containing electron dense material, indicating defects in autophagy or membrane processing, However, both LC3 expression and lipidation were normal both basally and on chloroquine treatment. A LOX-derived oxidized phospholipid, 12-hydroxyeicosatetraenoic acid-phosphatidylethanolamine (12-HETE-PE) was found to be a preferred substrate for yeast Atg8 lipidation, versus native PE, while both native and oxidized PE were effective substrates for LC3 lipidation. Last, phospholipidomics demonstrated altered levels of several phospholipid classes. Thus, we show that oxidized phospholipids generated by 12/15-LOX can act as substrates for key proteins required for effective autophagy and that cells deficient in this enzyme show evidence of autophagic dysfunction. The data functionally link phospholipid oxidation with autophagy for the first time.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Medicine Pharmacy Systems Immunity Research Institute (SIURI)
Subjects:	R Medicine > R Medicine (General)
Uncontrolled Keywords:	Lipid; Autophagy; Lipoxygenase; Mitochondria
Publisher:	Elsevier
ISSN:	2213-2317
Funders:	Wellcome Trust
Date of First Compliant Deposit:	30 March 2016
Date of Acceptance:	11 November 2014
Last Modified:	14 May 2024 15:26
URI:	https://orca.cardiff.ac.uk/id/eprint/69654

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