title: Involvement of mortalin/GRP75/mthsp70 in the mitochondrial impairments induced by A53T mutant α-synuclein.
abstract: Mutations and excessive accumulation of α-synuclein (α-syn) can lead to the degeneration of dopaminergic neurons, indicating a pivotal role of α-syn in the pathogenesis of Parkinson's disease (PD). Although how α-syn contributes to PD is still elusive, mitochondrial impairments have been reported to be implicated in. Mortalin, a molecular chaperone mainly located in mitochondria, has been linked to the pathogenesis of PD in recent studies. Moreover, some proteomics studies indicate that mortalin is associated with PD-related proteins, including α-syn. Therefore it is of interest to understand the function of mortalin in the mitochondrial disruption induced by A53T α-syn overexpression. The present study modulated the expression of mortalin and detected the effect of mortalin on the mitochondrial impairments induced by A53T α-syn in SH-SY5Y cells. Our data revealed that A53T α-syn could disrupt mitochondrial dynamics and increase the neuronal susceptibility to neurotoxin rotenone. The expression of mortalin decreased significantly in dopaminergic cells overexpressing A53T α-syn; furthermore, the down-regulation of mortalin could attenuate the disrupted mitochondrial dynamics by reducing α-syn translocation to mitochondria, suggesting that a compensatory mechanism of mortalin might be implicated in the pathogenesis of PD.
authors: Department of Neurology, Huashan Hospital Affiliated to Fudan University, 12 Wulumuqi Middle Road, Shanghai 200040, China; Department & Institute of Neurology, Shanghai Medical College, Fudan University, Shanghai 200040, China. Electronic address: liuft110@aliyun.com.
authors: Feng-Tao
authors: FT
authors: Liu
authors: Department of Neurology, Huashan Hospital Affiliated to Fudan University, 12 Wulumuqi Middle Road, Shanghai 200040, China; Department & Institute of Neurology, Shanghai Medical College, Fudan University, Shanghai 200040, China. Electronic address: chhyann@gmail.com.
authors: Yan
authors: Y
authors: Chen
authors: Department of Cellular and Genetic Medicine, School of Basic Medical Sciences, Fudan University, Shanghai 200032, China. Electronic address: yujieyang1015@me.com.
authors: Yu-Jie
authors: YJ
authors: Yang
authors: Department of Cellular and Genetic Medicine, School of Basic Medical Sciences, Fudan University, Shanghai 200032, China. Electronic address: yangling@fudan.edu.cn.
authors: Ling
authors: L
authors: Yang
authors: State Key Laboratory of Medical Neurobiology, School of Basic Medical Sciences, Fudan University, Shanghai 200032, China. Electronic address: yumei@fudan.edu.cn.
authors: Mei
authors: M
authors: Yu
authors: Department of Neurology, Huashan Hospital Affiliated to Fudan University, 12 Wulumuqi Middle Road, Shanghai 200040, China; Department & Institute of Neurology, Shanghai Medical College, Fudan University, Shanghai 200040, China. Electronic address: zhaojian20052006@163.com.
authors: Jian
authors: J
authors: Zhao
authors: Department of Neurology, Huashan Hospital Affiliated to Fudan University, 12 Wulumuqi Middle Road, Shanghai 200040, China; Department & Institute of Neurology, Shanghai Medical College, Fudan University, Shanghai 200040, China. Electronic address: jungliw@gmail.com.
authors: Jian-Jun
authors: JJ
authors: Wu
authors: State Key Laboratory of Medical Neurobiology, School of Basic Medical Sciences, Fudan University, Shanghai 200032, China; Institutes of Brain Science, Fudan University, Shanghai 200032, China. Electronic address: huangf@shmu.edu.cn.
authors: Fang
authors: F
authors: Huang
authors: Department of Cellular and Genetic Medicine, School of Basic Medical Sciences, Fudan University, Shanghai 200032, China. Electronic address: liuwen@shmu.edu.cn.
authors: Wen
authors: W
authors: Liu
authors: Department of Neurology, Huashan Hospital Affiliated to Fudan University, 12 Wulumuqi Middle Road, Shanghai 200040, China; Department & Institute of Neurology, Shanghai Medical College, Fudan University, Shanghai 200040, China. Electronic address: zhtding@hotmail.com.
authors: Zheng-Tong
authors: ZT
authors: Ding
authors: Department of Neurology, Huashan Hospital Affiliated to Fudan University, 12 Wulumuqi Middle Road, Shanghai 200040, China; Department & Institute of Neurology, Shanghai Medical College, Fudan University, Shanghai 200040, China. Electronic address: wangjian336@hotmail.com.
authors: Jian
authors: J
authors: Wang
mesh_terms: D045744:Cell Line, Tumor; D018840:HSP70 Heat-Shock Proteins / Q000096:biosynthesis* / Q000235:genetics; D006801:Humans; D008928:Mitochondria / Q000235:genetics / Q000378:metabolism*; D024101:Mitochondrial Proteins / Q000096:biosynthesis* / Q000235:genetics; D009154:Mutation; D010300:Parkinson Disease / Q000235:genetics / Q000378:metabolism; D021381:Protein Transport; D051844:alpha-Synuclein / Q000235:genetics* / Q000378:metabolism
chemical_list: D018840:HSP70 Heat-Shock Proteins; C492001:HSPA9 protein, human; D024101:Mitochondrial Proteins; D051844:alpha-Synuclein
keywords: A53T mutant α-synuclein; Mitochondrial dynamics; Mitochondrial translocation of α-synuclein; Mortalin; Parkinson׳s disease