BAG5 interacts with the Parkinson-associated protein PINK1 to protect against oxidative mitochondria

来源 :中国神经科学学会第九届全国学术会议暨第五届会员代表大会 | 被引量 : 0次 | 上传用户:liuhu8207
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  Mutations in PTEN-induced kinase 1 (PINK1) gene cause PARK6 familial Parkinsonism, and loss the stability of PINK1 may also contribute to sporadic Parkinsons disease (PD).Degradation of PINK1 occurs predominantly through the ubiquitin-proteasome pathway, however, to date, few of the proteins have been found to regulate the degradation of PINK1.Using the yeast two-hybrid system and pull-down methods, we identified bcl-2-associated athanogene 5 (BAG5), a BAG family member, directly interacted with P1NK1.We showed that BAG5 stabilized PINK1 by decreasing the ubiquitination of PINK1.Interestingly, BAG5 rescued MPP+-and rotenone-induced mitoehondria dysfunction by up-regulating PINK1 in vitro.In PINK1-null mice and MPTP-treated mice, significantly increased in the substantia nigra pars compacta (SNpc) although PINK1 was decreased.Moreover, rasagiline treatment to MPTP-treated mice resulted in further increase of BAG5 protein.In summary, we present BAG5 as a key protein to stabilize PINK1, thereby proventing mitochondrial dysfunction following oxidative stress.
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