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

Abstract

Parkinson’s disease (PD) is a multi-factorial 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 post-transcriptional gene regulation. MiR-7019-3p is encoded within the 5th intron of PD associated protein PINK1. In present study, we firstly demonstrated miR-7019-3p expression is significantly up regulated 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 OPA1 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-OPA1/12s rRNA, 16s rRNA and polycistronic RNA.Our results have suggested a promising and potential therapeutic target for reversing mitochondria dysregulation in neuronal cells during Parkinson's disease process.