"STRUCTURAL INTERACTIONS OF ALPHA­SYNUCLEIN WITH MITOCHONDRIA".

MARTINEZ J; FEDERICO FUENTES; GUAIMAS F; NEUMANN D; JAKOBS S; JOVIN T; JARES-ERIJMAN E

Huerta Grande - Córdoba

Congreso; XXVI Annual Meeting of the Argentine Society for Neurochemistry (SAN).; 2011

Sociedad Argentina de Investigación en Neurociencias (SAN)

Substantia Nigra. Alpha-Synuclein (AS) is a 15 KDa protein expressed in centralnervous system and is the major component of the protein aggregates in PD. Itwas proposed that in early steps of AS aggregation, toxic oligomeric species areformed that may lead to mitochondrial malfunction, fragmentation and apoptosis.The aim of this work is to characterize the interaction of AS with mitochondrialmembranes in intact organelles. Mitochondria were isolated from SH-SY5Y cellsand incubated with fluorescent labeled AS (0, 1 and 10μM). Outer membrane wasrevealed by immunofluorescence of TOM20. A combined study using confocal andwidefield microscopy with deconvolution and 3D reconstruction, reveals that thereis a different localization of AS dependent on the concentration. At 1 μM of AS theprotein colocalizes with TOM20 showing an outer membrane distribution. Whenmitochondria were incubated with 10μM AS, it localizes in the interior of theorganelle. STED microscopy shows that AS is distributed in clusters in the outermembrane, not revealed by the other tecniques. This results exhibit features on ASinteraction with mitochondria that may help to explain the malfunctions observedin PD.