Author: Rémi
Last saved by: Saritas, Sevim
Company: Hewlett-Packard Company

Role of Pex11p in Lipid Homeostasis in Yarrowia lipolytica
Dulermo Rémi^a, Dulermo Thierry^a, Heber Gamboa-Meléndez^a, Thevenieau France^b and Jean-Marc Nicaud^a#
^aINRA, UMR1319 Micalis, Jouy-en-Josas, F-78352, France
^bSOFIPROTEOL, Direction Innovation, 11 rue de Monceau, Paris, F-75378, France

Peroxisomes are essential organelles in the cells of all eukaryotes, from yeasts to mammals. Their role in β-oxidation is particularly essential in yeasts; for example, in Saccharomyces cerevisiae, fatty acid oxidation takes place solely in peroxisomes. In this species, peroxisome division occurs when lipids are present in the culture medium and is performed by the Pex11p protein family: ScPex11p, ScPex25p, ScPex27p, and ScPex34p. Yarrowia lipolytica has three Pex11p homologues, which are YALI0C04092p (YlPex11p), YALI0C04565p, and YALI0D25498p. We found that genes coding for these proteins were positively regulated by oleic acid, and as has been observed in other organisms, YlPEX11 deletion generated giant peroxisomes when mutant yeast were grown in an oleic acid medium. Moreover, ΔYlpex11 was unable to grow on fatty acid media and showed extreme dose-dependent sensitivity to oleic acid. Indeed, when the strain was grown in YNB with 0.5% glucose and 3% oleic acid, lipid body lysis and cell death were observed. The lysis of lipid bodies may be partially explained by an imbalance in the expression of the genes involved in lipid storage, namely DGA1, DGA2, and LRO1, as well as that of TGL4, which is involved in lipid remobilisation. TGL4 deletion and DGA2 overexpression resulted in decreased oleic acid sensitivity and delayed cell death in ΔYlpex11, which probably stemmed from the release of free fatty acids into the cytoplasm. All these results show that YlPex11p plays an important role in lipid homeostasis in Y. lipolytica.