Alpha-synuclein interaction with mitochondria is dynamic and affects mitochodrial function

MARTINEZ JIMENA H; FUENTES FEDERICO; VANASCO VIRGINIA; ALVAREZ SILVIA; JOVIN TOM

Buenos Aires

Congreso; VIII International Congress of SFRBM South American Group.; 2013

Society for Free Radical Biology and Medicine

Parkinson?s disease (PD) is a neurodegenerative disorder that affects 1% of the population over 60 years. Alpha-synuclein (AS) over-expression and its interaction with mitochondria are implicated in the development of PD. Isolated mitochondria from rat brain were incubated with AS (0 to 100 μM); oxygen consumption was measured and its effect on respiratory chain activity was evaluated. Oxygen consumption decreased by 30 % (N = 3) when mitochondria were incubated with AS 100 uM compared to control mitochondria. Mitochondrial fractionation and microscopy showed a concentration-dependent AS association with rat brain and SHSY5Y cells mitochondria after 30 min of incubation with the labeled protein. This association was found to be dynamic. Post- incubation washing showed an important decrease of binding (> 50% after 30 min) and further incubation with AS showed an increase in the AS signals. In conclusion, we suggest that the interaction of AS with mitochondria results in a decrease of cellular respiration that could lead to an impairment of mitochondrial respiration and cell death in PD.