IQUIBICEN   23947
INSTITUTO DE QUIMICA BIOLOGICA DE LA FACULTAD DE CIENCIAS EXACTAS Y NATURALES
Unidad Ejecutora - UE
artículos
Título:
Alpha-synuclein mitochondrial interaction leads to irreversible translocation and complex I impairment
Autor/es:
VELAZQUEZ, FRANCISCO; ALAIMO, AGUSTINA; FUENTES, FEDERICO; CASSINA, ADRIANA; VANASCO, VIRGINIA; COLUCCIO LESKOW, FEDERICO; ALVAREZ, SILVIA; MARTÍNEZ, JIMENA H.
Revista:
ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS
Editorial:
ELSEVIER SCIENCE INC
Referencias:
Año: 2018 vol. 651 p. 1 - 12
ISSN:
0003-9861
Resumen:
α-synuclein is involved in both familial and sporadic Parkinson´s disease. Although its interaction with mitochondria has been well documented, several aspects remains unknown or under debate such as the specific sub-mitochondrial localization or the dynamics of the interaction. It has been suggested that α-synuclein could only interact with ER-associated mitochondria. The vast use of model systems and experimental conditions makes difficult to compare results and extract definitive conclusions. Here we tackle this by analyzing, in a simplified system, the interaction between purified α-synuclein and isolated rat brain mitochondria. This work shows that wild type α-synuclein interacts with isolated mitochondria and translocates into the mitochondrial matrix. This interaction and the irreversibility of α-synuclein translocation depend on incubation time and α-synuclein concentration. FRET experiments show that α-synuclein localizes close to components of the TOM complex suggesting a passive transport of α-synuclein through the outer membrane. In addition, α-synuclein binding alters mitochondrial function at the level of Complex I leading to a decrease in ATP synthesis and an increase of ROS production.