Subcellular localization and function analysis of PINK1 mitron in PD progression: Mitron modulates mitochondrial morphology to regulate neuronal death

PINK1 mitron 在 PD 进展中的亚细胞定位和功能分析:Mitron 调节线粒体形态以调节神经元死亡

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作者:Yu Qiao, Jiayuan Kou, Ye Tian, Wenkai Ma, Yang Yu, Jingjing Pang, Yingting Pei, Yu Zhang, Bin Ye, Ziying Xie, Jinying Liu, Zhihui Wang, Lujing Wang, Xu Gao, Ning Ma, Yanfen Zhang

Abstract

Parkinson's disease (PD) is a multifactorial neurodegenerative disorder. Loss or degeneration of the dopaminergic neurons in the substantia nigra and development of Lewy bodies in dopaminergic neurons were the defining pathologic changes. MiRNAs fine-tune the protein levels by posttranscriptional gene regulation. MiR-7019-3p is encoded within the fifth intron of PD-associated protein PINK1. In present study, we firstly demonstrated miR-7019-3p expression is significantly upregulated in PD mice model and neuron cell models, miR-7019-3p mainly existed in mitochondria, miR-7019-3p could regulate the structure, and function of mitochondria in neuronal cells. We predicted and verified that mitochondria-associated protein optic atrophy 1 and 12s rRNA, 16s rRNA, and polycistronic RNA are target genes of miR-7019-3p. Finally, we proved that SP1 protein could independently regulate the expression of miR-7019-3p at the upstream. The evidences in the study suggest the role miR-7019-3p in the regulation of mitochondrial structure and function, and this kind of regulation could be implemented or promoted through the pathway of SP1-miR-7019-3p-optic atrophy 1/12s rRNA, 16s rRNA, and polycistronic RNA. Our results have suggested a promising and potential therapeutic target for reversing mitochondria dysregulation in neuronal cells during PD process.

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