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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2018
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| Acceso en línea: | https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_00039861_v651_n_p1_Martinez http://hdl.handle.net/20.500.12110/paper_00039861_v651_n_p1_Martinez |
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paper:paper_00039861_v651_n_p1_Martinez2023-06-08T14:25:07Z Alpha-synuclein mitochondrial interaction leads to irreversible translocation and complex I impairment 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 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 2018 https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_00039861_v651_n_p1_Martinez http://hdl.handle.net/20.500.12110/paper_00039861_v651_n_p1_Martinez |
| institution |
Universidad de Buenos Aires |
| institution_str |
I-28 |
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R-134 |
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Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA) |
| topic |
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 |
| spellingShingle |
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 Alpha-synuclein mitochondrial interaction leads to irreversible translocation and complex I impairment |
| topic_facet |
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 |
| description |
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 |
| title |
Alpha-synuclein mitochondrial interaction leads to irreversible translocation and complex I impairment |
| title_short |
Alpha-synuclein mitochondrial interaction leads to irreversible translocation and complex I impairment |
| title_full |
Alpha-synuclein mitochondrial interaction leads to irreversible translocation and complex I impairment |
| title_fullStr |
Alpha-synuclein mitochondrial interaction leads to irreversible translocation and complex I impairment |
| title_full_unstemmed |
Alpha-synuclein mitochondrial interaction leads to irreversible translocation and complex I impairment |
| title_sort |
alpha-synuclein mitochondrial interaction leads to irreversible translocation and complex i impairment |
| publishDate |
2018 |
| url |
https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_00039861_v651_n_p1_Martinez http://hdl.handle.net/20.500.12110/paper_00039861_v651_n_p1_Martinez |
| _version_ |
1768543634818334720 |