Abstract: Objective: The purpose of this study is to exam the changes of mitochondrial membrane induced by overexpressing α-syn, α-syn /N, NAC domain and α-syn /C domain in MN9D cells. Methods: Transiently transfected various domains of α-syn gene into MN9D cells. The MN9D cell’s viability was observed by MTT assay and release of LDH respectively. The reactive oxygen species (ROS) level, mitochondrial permeability pore (mPTP) and mitochondrial membrane potential (ΔΨm) were examined by confocal image and flow cytometry, the morphology of mitochondria was examined by confocal image. Results: Overexpressing α-syn，α-syn/N，α-syn/delC could induce the decrease of cell viability. The LDH release was increased by α-syn，α-syn/N，α-syn/delC (p <0.01). A-syn，α-syn/N，α-syn/delC could increase the ROS level（p<0.001）,decrease mitochondrial membrane potential (p <0.01）and increase the opening of mPTP（p <0.01）.The result of confocal microscopy showed that 55% mitochondria of HEK293T cells overexpressing α-syn/N had so-called balloon phenotype. Conclusions: Amino-terminus of α-synuclein induces mitochondrial membrane injuries.

Key words: α-synuclein, α-syn /N, ROS, mitochondrial membrane potential (ΔΨm), mitochondrial permeability pore (mPTP)