Alpha-synuclein mitochondrial interaction leads to irreversible translocation and complex I impairment

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 sug...

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Autor principal: Martínez, J.H
Otros Autores: Fuentes, F., Vanasco, V., Alvarez, S., Alaimo, A., Cassina, A., Coluccio Leskow, F., Velazquez, F.
Formato: Capítulo de libro
Lenguaje:Inglés
Publicado: Academic Press Inc. 2018
Acceso en línea:Registro en Scopus
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024 7 |2 cas  |a 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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030 |a ABBIA 
100 1 |a Martínez, J.H. 
245 1 0 |a Alpha-synuclein mitochondrial interaction leads to irreversible translocation and complex I impairment 
260 |b Academic Press Inc.  |c 2018 
270 1 0 |m Velazquez, F.; CONICET, Universidad de Buenos Aires, Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales (IQUIBICEN)Argentina; email: fvelazquez@qb.fcen.uba.ar 
506 |2 openaire  |e Política editorial 
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520 3 |a 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  |l eng 
536 |a Detalles de la financiación: Universidad de Buenos Aires, PIP 11220110100573 
536 |a Detalles de la financiación: To the memory of Dr. Elizabeth Jares-Erijman, who was supervisor of JHM and first envisioned this project. We acknowledge Professor Thomas Jovin for financial support, and supervision of the work at early stages. This research was supported by Projects UBACyT 20020100100465BA and UBACyT 20020130200025BA from Universidad de Buenos Aires , and PIP 11220110100573 from CONICET of Argentina. Appendix A 
593 |a Universidad de Buenos Aires, Facultad de Ciencias Exactas y Naturales, Departamento de Química Biológica, Buenos Aires, Argentina 
593 |a CONICET, Universidad de Buenos Aires, Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales (IQUIBICEN), Buenos Aires, Argentina 
593 |a Instituto de Medicina Experimental- IMEX, CONICET, Academia Nacional de Medicina, Buenos Aires, Argentina 
593 |a Instituto de Bioquímica y Medicina Molecular (IBIMOL), Universidad de Buenos Aires, Argentina 
593 |a CEINBIO, Depto. Bioquímica, Facultad de Medicina, Universidad de la Republica, Montevideo, Uruguay 
593 |a Universidad de Buenos Aires, Facultad de Ciencias Exactas y Naturales, Departamento de Fisiología, Biología Molecular y Celular, Buenos Aires, Argentina 
690 1 0 |a MITOCHONDRIA 
690 1 0 |a MITOCHONDRIAL METABOLISM 
690 1 0 |a PARKINSON'S DISEASE 
690 1 0 |a Α-SYNUCLEIN 
690 1 0 |a ADENOSINE TRIPHOSPHATE 
690 1 0 |a ALPHA SYNUCLEIN 
690 1 0 |a REACTIVE OXYGEN METABOLITE 
690 1 0 |a RECOMBINANT PROTEIN 
690 1 0 |a REDUCED NICOTINAMIDE ADENINE DINUCLEOTIDE DEHYDROGENASE (UBIQUINONE) 
690 1 0 |a TRANSLOCASE OF OUTER MITOCHONDRIAL MEMBRANE 20 
690 1 0 |a ADULT 
690 1 0 |a ANIMAL CELL 
690 1 0 |a ANIMAL EXPERIMENT 
690 1 0 |a ANIMAL TISSUE 
690 1 0 |a ARTICLE 
690 1 0 |a BRAIN MITOCHONDRION 
690 1 0 |a CELL ISOLATION 
690 1 0 |a CONTROLLED STUDY 
690 1 0 |a ELECTRON TRANSPORT 
690 1 0 |a FLUORESCENCE RESONANCE ENERGY TRANSFER 
690 1 0 |a MALE 
690 1 0 |a MITOCHONDRIAL MEMBRANE POTENTIAL 
690 1 0 |a MITOCHONDRIAL RESPIRATION 
690 1 0 |a NONHUMAN 
690 1 0 |a NUCLEIC ACID SYNTHESIS 
690 1 0 |a OUTER MEMBRANE 
690 1 0 |a PASSIVE TRANSPORT 
690 1 0 |a PRIORITY JOURNAL 
690 1 0 |a PROTEIN INTERACTION 
690 1 0 |a PROTEIN LOCALIZATION 
690 1 0 |a PROTEIN PURIFICATION 
690 1 0 |a PROTEIN TRANSPORT 
690 1 0 |a RAT 
690 1 0 |a RESPIRATORY CHAIN 
700 1 |a Fuentes, F. 
700 1 |a Vanasco, V. 
700 1 |a Alvarez, S. 
700 1 |a Alaimo, A. 
700 1 |a Cassina, A. 
700 1 |a Coluccio Leskow, F. 
700 1 |a Velazquez, F. 
773 0 |d Academic Press Inc., 2018  |g v. 651  |h pp. 1-12  |p Arch. Biochem. Biophys.  |x 00039861  |w (AR-BaUEN)CENRE-1377  |t Archives of Biochemistry and Biophysics 
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