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

Alwena Morgan , Victoria Hammond , Machiko Sakoh-Nakatogawa , Yoshinori Ohsumi (1) , Christopher Thomas , Fabien P. Blanchet (2) , Vincent Piguet (3) , Kirill Kiselyov (4) , Valerie O’donnell

1 Frontier Research Center
2 IRIM - Institut de Recherche en Infectiologie de Montpellier
3 Division of Infection and Immunity
4 department of biological sciences, University of Pittsburg

12/15-Lipoxygenase (LOX) enzymatically generates oxidized phospholipids in monocytes and macro-phages. 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-phosphatidylethano-lamine (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.

Domaines: Biologie cellulaire; Immunologie; Virologie; Immunité innée; Immunité adaptative

Alwena Morgan, Victoria Hammond, Machiko Sakoh-Nakatogawa, Yoshinori Ohsumi, Christopher Thomas, et al.. A novel role for 12/15-lipoxygenase in regulating autophagy. Redox Biology, 2015, 4, pp.40-47. ⟨10.1016/j.redox.2014.11.005⟩. ⟨hal-02352193⟩