CONICET | Buscador de Institutos y Recursos Humanos

The P-type ion pumps are membrane transporters energizedby ATP-hydrolysis.They were classiﬁed into ﬁvesubfamilies termed P1-P5; the substrate speciﬁcity of P5 subfamily isstill unknown. Five genes named ATP13A1-ATP13A5 that belongtothe P5-ATPases are present in humans. Mutations of the ATP13A2 gene, also known as PARK9, were initially associated with a form of Parkinson?s Disease (PD),a form of NCL (CNL12) and of hereditaryspastic paraplegia (SPG78) ATP13A2 islocalized in lysosomes and late endosomes (LEs). Dysfunction of this proteindiminishes the lysosomal degradation, the autophagic ﬂux and the exosome externalization. We have previously shown that ATP13A2 expression caused a reduction of the iron-induced lysosome membrane permeabilization, whichsuggests that ATP13A2 overexpression improves the lysosome and LE membrane integrity. In this work, we stably expressed the ATP13A2 in SH-SY5Y humanneuroblastoma cell line. By ﬂuorescence microscopy, we found that the expressionof ATP13A2 increases the accumulation of the ﬂuorescent analog phosphatidylethanolamine (NBD-PE) while reduces the accumulation of ceramide(NBD-ceramide). Inimmunoﬂuorescenceassays, we found that the expressionofATP13A2 reduces the content of bis(monoacylglyceryl)phosphate (BMP).Besides, the triglyceride and cholesterol contentis reduced in ATP13A2-expressing cells,while the synthesis ofpolar lipids is increased. Altogetherthese results show that ATP13A2 overexpression modiﬁes the lipid homeostasis inSH-SY5Y cells. As BMP is required for the lipid degradation process and the exosome biogenesis inside theacidic compartments, these resultssuggestthat ATP13A2 may be modifying the lipid digestion capacity and/or the redistribution of lipids in these subcellularorganelles