Identification of the mitochondria-related gene IRF7 shared by physical exercise and Parkinson's disease and exploration of its potential molecular mechanisms.

BACKGROUND: Physical exercise (PE) holds significant clinical value in alleviating the progression of Parkinson's disease (PD), yet its underlying regulatory mechanisms remain unclear. Our study aims to investigate the role of mitochondria-related genes in the regulatory mechanisms by which physical exercise ameliorates Parkinson's disease. METHODS: Mitochondria-related differentially expressed genes (DEGs) were screened via differentially expressed gene analysis. Least Absolute Shrinkage and Selection Operator (LASSO) regression analysis and a random forest algorithm were applied for dimensionality reduction and screening of the mitochondria-related hub genes. The diagnostic efficacy of mitochondria-related genes was evaluated using a nomogram model and receiver operating characteristic (ROC) curves. Reverse transcription-quantitative polymerase chain reaction (RT-qPCR), flow cytometry and confocal microscopy technique were employed to validate the expression of interferon regulatory factor 7 (IRF7) and explore its functional mechanism in in vitro cellular experiments. RESULTS: Our findings demonstrated that IRF7 was significantly upregulated in PD and exhibited favorable diagnostic value (AUC = 0.875). We identified that RelA might serve as a potential transcription factor for IRF7. Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis indicated a positive correlation between IRF7 expression and the ferroptosis pathway. Additionally, PE effectively downregulated IRF7 expression. Furthermore, the expression of CD4+ memory resting T cells was positively correlated with IRF7 in PD. In vitro experiments showed that IRF7 can regulate intracellular lipid ROS production, ATP levels, mitochondrial morphology and expression of ferroptosis-related genes in PD cell model. CONCLUSIONS: PE can potentially downregulate the expression of the mitochondria-related gene IRF7, regulate the ferroptosis pathway, and thereby interfere with the progression of PD. This study provides novel insights into the potential mechanisms underlying PE-mediated prevention of PD.