IQUIBICEN   23947
INSTITUTO DE QUIMICA BIOLOGICA DE LA FACULTAD DE CIENCIAS EXACTAS Y NATURALES
Unidad Ejecutora - UE
artículos
Título:
Mitochondrial interaction of alpha-synuclein leads to irreversible translocation and complex I impairment
Autor/es:
VELAZQUEZ, FRANCISCO; ALAIMO, AGUSTINA; FUENTES, FEDERICO; LESKOW, FEDERICO COLUCCIO; ALVAREZ, SILVIA; CASSINA, ADRIANA; MARTÍNEZ, JIMENA H.; VANASCO, VIRGINIA
Revista:
ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS
Editorial:
ELSEVIER SCIENCE INC
Referencias:
Lugar: Amsterdam; Año: 2018
ISSN:
0003-9861
Resumen:
a-synuclein is involved in both familial and sporadic Parkinson?s disease. Although its interaction withmitochondria has been well documented several aspects remains unknown or under debate; such as thespecific sub-mitochondrial localization of a-synuclein or the dynamics of the interaction. It has beensuggested that a-synuclein could only interact with ER-associated mitochondria. Variety of model systemsand experimental conditions makes difficult to compare results and extract definitive conclusions. Here wetackle these issues and analyze this interaction in a simplified model system consisting of purified a-synuclein and isolated rat brain mitochondria. This work shows that wild type a-synuclein interacts withisolated mitochondria without the need of any other cellular component and it is able to translocate intomitochondrial matrix. We present as well that this interaction and the irreversibility of the a-synucleintranslocation depend on the time of incubation and a-synuclein concentration. FRET experiments show thata-synuclein localizes close to components of the TOM complex what it would be compatible with a passivetransport of a-synuclein through the outer membrane. In addition, we describe how a-synuclein bindingalters mitochondrial function at the level of Complex I what correlates with a decrease in ATP synthesis andan increase of ROS production.