IQUIFIB   02644
INSTITUTO DE QUIMICA Y FISICOQUIMICA BIOLOGICAS "PROF. ALEJANDRO C. PALADINI"
Unidad Ejecutora - UE
artículos
Título:
The Parkinson-associated human P5B-ATPase ATP13A2 modifies lipid homeostasis
Autor/es:
MARCOS, ALEJANDRA LUCÍA; CASALI, CECILIA IRENE; MAZZITELLI, LUCIANA ROMINA; DE TEZANOS PINTO, FELICITAS; ADAMO, HUGO PEDRO; MAZZITELLI, LUCIANA ROMINA; CORRADI, GERARDO RAUL; ADAMO, HUGO PEDRO; CORRADI, GERARDO RAUL; DEL CARMEN FERNÁNDEZ TOME, MARÍA; DEL CARMEN FERNÁNDEZ TOME, MARÍA; MARCOS, ALEJANDRA LUCÍA; CASALI, CECILIA IRENE; DE TEZANOS PINTO, FELICITAS
Revista:
BIOCHIMICA ET BIOPHYSICA ACTA-BIOMEMBRANES
Editorial:
ELSEVIER SCIENCE BV
Referencias:
Año: 2019
ISSN:
0005-2736
Resumen:
Mutations in the ATP13A2 gene (PARK9, CLN12, OMIM 610513) were initially associated with a form of Parkinson?s Disease (PD) known as Kufor Rakeb Syndrome (KRS). However, the genetic spectrum of ATP13A2-associated disorders was expanded in the last years, because it has been found to underlay variants of neuronal ceroid-lipofuscinoses (NCLs) and hereditary spastic paraplegia. As ATP13A2 seems to be a key component of the endo-lysosome pathway, the factthat these pathologies are commonly characterized by endo-lysosomal dysfunction is not surprising.Here we report that increasing the level of functional ATP13A2 in a stable SH-SY5Y cell line disrupts lipid homeostasis. ATP13A2 overexpression increases the fluorescence intensity of the fluorescent analog phosphatidylethanolamine (NBD-PE) and the formation of multilamellar bodies, resembling the so-called ?drug-induced phospholipidosis?. We also found that expression of ATP13A2 reduces the ceramide-fluorescence intensity and the content of bis(monoacylglyceryl)phosphate (BMP). BMP is required for lipid degradation and exosome biogenesis inside acidic compartments, so this result suggests that ATP13A2 may be modifying the lipid digestion capacity and/or the redistribution of lipids in these subcellular organelles. In addition, ATP13A2-overexpression decreased the total content of triglycerides (TGs), cholesterol and lipid droplets. As TGs are necessary for the synthesis of new membranes, this observation suggests that increasing the function of ATP13A2 switches the endo-lysosomal system towards vesicle secretion.