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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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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