The Parkinson-associated human P5B-ATPase ATP13A2 modifies lipid homeostasis

Publication date: Available online 24 May 2019Source: Biochimica et Biophysica Acta (BBA) - BiomembranesAuthor(s): Alejandra Lucía Marcos, Gerardo Raul Corradi, Luciana Romina Mazzitelli, Cecilia Irene Casali, María del Carmen Fernández Tome, Hugo Pedro Adamo, Felicitas de Tezanos PintoAbstractMutations 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 fact that 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 digesti...

Source: Biochimica et Biophysica Acta (BBA) Biomembranes - May 25, 2019 Category: Biochemistry Source Type: research