P5-ATPase ATP13A2-overexpression in SH-SY5Y cells modifies the lipid homeostasis

MARCOS, ALEJANDRA; MAZZITELLI,LUCIANA ROMINA; GERARDO R CORRADI; FELICITAS DE TEZANOS PINTO; SOLIS PAVESIO, LOURDES; HUGO PEDRO ADAMO

Congreso; XLVII Reunión Anual de la Sociedad Argentina de Biofísica; 2018

Sociedad Argentina de Biofísica

AbstractThe P-type ion pumps are membrane transporters energized by ATP-hydrolysis.They were classified into five subfamilies termed P1-P5; the substrate specificity of P5 subfamily is still unknown. Five genes named ATP13A1-ATP13A5 that belong to the 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 hereditary spastic paraplegia (SPG78) ATP13A2 is localized in lysosomes and late endosomes (LEs). Dysfunction of this protein diminishes 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, which suggests that ATP13A2 overexpression improves the lysosome and LE membrane integrity. In this work, we stably expressed the ATP13A2 in SH-SY5Y human neuroblastoma cell line. By fluorescence microscopy, we found that the expression of ATP13A2 increases the accumulation of the fluorescent analogphosphatidylethanolamine (NBD-PE) while reduces the accumulation of ceramide(NBD-ceramide). In immunofluorescence assays, we found that the expression ofATP13A2 reduces the content of bis(monoacylglyceryl)phosphate (BMP). Besides,the triglyceride and cholesterol content is reduced in ATP13A2-expressing cells,while the synthesis of polar lipids is increased. Altogether these results show that ATP13A2 overexpression modifies the lipid homeostasis in SH-SY5Y cells. As BMP is required for the lipid degradation process and the exosome biogenesis inside the acidic compartments, these results suggest that ATP13A2 may be modifying the lipid digestion capacity and/or the redistribution of lipids in these subcellular organelles.