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Involvement of mortalin/GRP75/mthsp70 in the mitochondrial impairments induced by A53T mutant α-synuclein.
Brain Res. 2015 Apr 16; 1604:52-61.BR

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.

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Authors+Show Affiliations

Liu FT
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.
Chen Y
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.
Yang YJ
Department of Cellular and Genetic Medicine, School of Basic Medical Sciences, Fudan University, Shanghai 200032, China. Electronic address: yujieyang1015@me.com.
Yang L
Department of Cellular and Genetic Medicine, School of Basic Medical Sciences, Fudan University, Shanghai 200032, China. Electronic address: yangling@fudan.edu.cn.
Yu M
State Key Laboratory of Medical Neurobiology, School of Basic Medical Sciences, Fudan University, Shanghai 200032, China. Electronic address: yumei@fudan.edu.cn.
Zhao J
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.
Wu JJ
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.
Huang F
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.
Liu W
Department of Cellular and Genetic Medicine, School of Basic Medical Sciences, Fudan University, Shanghai 200032, China. Electronic address: liuwen@shmu.edu.cn.
Ding ZT
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.
Wang J
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.

MeSH

Cell Line, TumorHSP70 Heat-Shock ProteinsHumansMitochondriaMitochondrial ProteinsMutationParkinson DiseaseProtein Transportalpha-Synuclein

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

25665531

Citation

Liu, Feng-Tao, et al. "Involvement of mortalin/GRP75/mthsp70 in the Mitochondrial Impairments Induced By A53T Mutant Α-synuclein." Brain Research, vol. 1604, 2015, pp. 52-61.
Liu FT, Chen Y, Yang YJ, et al. Involvement of mortalin/GRP75/mthsp70 in the mitochondrial impairments induced by A53T mutant α-synuclein. Brain Res. 2015;1604:52-61.
Liu, F. T., Chen, Y., Yang, Y. J., Yang, L., Yu, M., Zhao, J., Wu, J. J., Huang, F., Liu, W., Ding, Z. T., & Wang, J. (2015). Involvement of mortalin/GRP75/mthsp70 in the mitochondrial impairments induced by A53T mutant α-synuclein. Brain Research, 1604, 52-61. https://doi.org/10.1016/j.brainres.2015.01.050
Liu FT, et al. Involvement of mortalin/GRP75/mthsp70 in the Mitochondrial Impairments Induced By A53T Mutant Α-synuclein. Brain Res. 2015 Apr 16;1604:52-61. PubMed PMID: 25665531.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Involvement of mortalin/GRP75/mthsp70 in the mitochondrial impairments induced by A53T mutant α-synuclein. AU - Liu,Feng-Tao, AU - Chen,Yan, AU - Yang,Yu-Jie, AU - Yang,Ling, AU - Yu,Mei, AU - Zhao,Jian, AU - Wu,Jian-Jun, AU - Huang,Fang, AU - Liu,Wen, AU - Ding,Zheng-Tong, AU - Wang,Jian, Y1 - 2015/02/07/ PY - 2014/08/13/received PY - 2014/12/23/revised PY - 2015/01/31/accepted PY - 2015/2/11/entrez PY - 2015/2/11/pubmed PY - 2016/1/20/medline KW - A53T mutant α-synuclein KW - Mitochondrial dynamics KW - Mitochondrial translocation of α-synuclein KW - Mortalin KW - Parkinson׳s disease SP - 52 EP - 61 JF - Brain research JO - Brain Res VL - 1604 N2 - 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. SN - 1872-6240 UR - https://www.unboundmedicine.com/medline/citation/25665531/Involvement_of_mortalin/GRP75/mthsp70_in_the_mitochondrial_impairments_induced_by_A53T_mutant_��_synuclein_ DB - PRIME DP - Unbound Medicine ER -