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

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

  • PeerJ. 2026 Mar 26:14:e20994. doi: 10.7717/peerj.20994.
Xinyi Hu # 1,  Zhiliang Cai # 2,  Feiran Zhou 3,  Siliang Chen 4,  Ping Li 5,  Siyi Jin 6,  Songyao Lan 7,  Xiaoyan Du 8,  Rui Xing 1
Affiliations

Affiliations

  • 1 Department of Intensive Care Unit, The Affiliated Guangdong Second Provincial General Hospital of Jinan University, Guangzhou, China.
  • 2 Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, China.
  • 3 Patient Monitoring and Life Support User Service Department, Shenzhen Mindray Bio-Medical Electronics Co., Ltd., Shenzhen, China.
  • 4 Department of Interventional Radiology, The Affiliated Guangdong Second Provincial General Hospital of Jinan University, Guangzhou, China.
  • 5 Department of Endocrinology, The Affiliated Guangdong Second Provincial General Hospital of Jinan University, Guangzhou, China.
  • 6 Medical Department, The Affiliated Guangdong Second Provincial General Hospital of Jinan University, Guangzhou, China.
  • 7 Department of Pathology, The Affiliated Guangdong Second Provincial General Hospital of Jinan University, Guangzhou, China.
  • 8 Department of General Medicine, The Affiliated Guangdong Second Provincial General Hospital of Jinan University, Guangzhou, China.
  • # Contributed equally.
PMID: 41913932 DOI: 10.7717/peerj.20994
Abstract

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.

Keywords

Ferroptosis; IRF7; Mitochondrial dysfunction; Parkinson’s disease; Physical exercise.

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