Martínez, J.H.; Fuentes, F.; Vanasco, V.; Alvarez, S.; Alaimo, A.; Cassina, A.; Coluccio Leskow, F.; Velazquez, F. "Alpha-synuclein mitochondrial interaction leads to irreversible translocation and complex I impairment" (2018) Archives of Biochemistry and Biophysics. 651:1-12
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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. © 2018


Documento: Artículo
Título:Alpha-synuclein mitochondrial interaction leads to irreversible translocation and complex I impairment
Autor:Martínez, J.H.; Fuentes, F.; Vanasco, V.; Alvarez, S.; Alaimo, A.; Cassina, A.; Coluccio Leskow, F.; Velazquez, F.
Filiación:Universidad de Buenos Aires, Facultad de Ciencias Exactas y Naturales, Departamento de Química Biológica, Buenos Aires, Argentina
CONICET, Universidad de Buenos Aires, Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales (IQUIBICEN), Buenos Aires, Argentina
Instituto de Medicina Experimental- IMEX, CONICET, Academia Nacional de Medicina, Buenos Aires, Argentina
Instituto de Bioquímica y Medicina Molecular (IBIMOL), Universidad de Buenos Aires, Argentina
CEINBIO, Depto. Bioquímica, Facultad de Medicina, Universidad de la Republica, Montevideo, Uruguay
Universidad de Buenos Aires, Facultad de Ciencias Exactas y Naturales, Departamento de Fisiología, Biología Molecular y Celular, Buenos Aires, Argentina
Palabras clave:Mitochondria; Mitochondrial metabolism; Parkinson's disease; α-synuclein; adenosine triphosphate; alpha synuclein; reactive oxygen metabolite; recombinant protein; reduced nicotinamide adenine dinucleotide dehydrogenase (ubiquinone); translocase of outer mitochondrial membrane 20; adult; animal cell; animal experiment; animal tissue; Article; brain mitochondrion; cell isolation; controlled study; electron transport; fluorescence resonance energy transfer; male; mitochondrial membrane potential; mitochondrial respiration; nonhuman; nucleic acid synthesis; outer membrane; passive transport; priority journal; protein interaction; protein localization; protein purification; protein transport; rat; respiratory chain
Página de inicio:1
Página de fin:12
Título revista:Archives of Biochemistry and Biophysics
Título revista abreviado:Arch. Biochem. Biophys.
CAS:adenosine triphosphate, 15237-44-2, 56-65-5, 987-65-5; alpha synuclein, 154040-18-3; reduced nicotinamide adenine dinucleotide dehydrogenase (ubiquinone), 9028-04-0


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---------- APA ----------
Martínez, J.H., Fuentes, F., Vanasco, V., Alvarez, S., Alaimo, A., Cassina, A., Coluccio Leskow, F.,..., Velazquez, F. (2018) . Alpha-synuclein mitochondrial interaction leads to irreversible translocation and complex I impairment. Archives of Biochemistry and Biophysics, 651, 1-12.
---------- CHICAGO ----------
Martínez, J.H., Fuentes, F., Vanasco, V., Alvarez, S., Alaimo, A., Cassina, A., et al. "Alpha-synuclein mitochondrial interaction leads to irreversible translocation and complex I impairment" . Archives of Biochemistry and Biophysics 651 (2018) : 1-12.
---------- MLA ----------
Martínez, J.H., Fuentes, F., Vanasco, V., Alvarez, S., Alaimo, A., Cassina, A., et al. "Alpha-synuclein mitochondrial interaction leads to irreversible translocation and complex I impairment" . Archives of Biochemistry and Biophysics, vol. 651, 2018, pp. 1-12.
---------- VANCOUVER ----------
Martínez, J.H., Fuentes, F., Vanasco, V., Alvarez, S., Alaimo, A., Cassina, A., et al. Alpha-synuclein mitochondrial interaction leads to irreversible translocation and complex I impairment. Arch. Biochem. Biophys. 2018;651:1-12.