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Detection of Disease-associated α-synuclein by Enhanced ELISA in the Brain of Transgenic Mice Overexpressing Human A53T Mutated α-synuclein
Published on: May 30, 2015
Localization of alpha-synuclein to mitochondria within midbrain of mice
Wen-Wei Li1, Ru Yang, Jing-Chun Guo
1Laboratory for Neurological Research of the Institute of Integrative Medicine, Zhongshan Hospital, People's Republic of China. wenweili2000@yahoo.com.cn
Abstract:
The interrelationship between alpha-synuclein (alpha-syn) and mitochondria is not clearly understood. Owing to the lack of the signal peptide and its predominant localization in the cytosol, alpha-syn is generally considered to affect mitochondrial function through some secondary effects. Contrary to this assumption, here, we show that a portion of alpha-syn is present in the membrane of mitochondria in normal dopaminergic neurons. The same profile is also found in other alpha-syn-positive neurons. Thus, binding to the membrane of mitochondria is the physiological nature of alpha-syn and might also contribute to the pathological role of this protein in the mitochondrial dysfunction in Parkinson's disease.
Insights
Alpha-synuclein (alpha-syn) is found in mitochondria membranes, challenging the view it only affects mitochondria indirectly. This direct interaction may play a role in Parkinson's disease mitochondrial dysfunction.
Area of Science:
- Neuroscience
- Cell Biology
- Biochemistry
Background:
- The relationship between alpha-synuclein (alpha-syn) and mitochondria is poorly understood.
- Alpha-synuclein is typically found in the cytosol and thought to affect mitochondria indirectly.
Purpose of the Study:
- To investigate the direct interaction of alpha-synuclein with mitochondria.
- To determine if alpha-synuclein's presence in mitochondria is a physiological or pathological phenomenon.
Main Methods:
- Immunofluorescence microscopy of dopaminergic neurons.
- Analysis of alpha-synuclein localization in neuronal tissues.
Main Results:
- A portion of alpha-synuclein was detected in the mitochondrial membrane of normal dopaminergic neurons.
- This mitochondrial membrane localization of alpha-synuclein was also observed in other alpha-synuclein-positive neurons.
Conclusions:
- Mitochondrial membrane binding is a physiological characteristic of alpha-synuclein.
- This direct interaction may contribute to mitochondrial dysfunction observed in Parkinson's disease.

