Martinez 2018 Arch Biochem Biophys

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Martínez JH, 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. Arch Biochem Biophys 651:1-12.

» PMID: 29702063

Martinez JH, Fuentes F, Vanasco V, Alvarez S, Alaimo A, Cassina A, Coluccio Leskow F, Velazquez F (2018) Arch Biochem Biophys

Abstract: α-synuclein is involved in both familial and sporadic Parkinson's disease. Although its interaction with mitochondria has been well documented, several aspects remain 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 it 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.

Keywords: Mitochondria, Mitochondrial metabolism, Parkinson's disease, α-synuclein Bioblast editor: Kandolf G

Labels: MiParea: Respiration  Pathology: Parkinson's 

Organism: Rat  Tissue;cell: Nervous system  Preparation: Isolated mitochondria 

Coupling state: LEAK, OXPHOS, ET  Pathway: N, S, ROX  HRR: Oxygraph-2k 

Labels, 2018-07