Transcriptomic Identification of Mitochondrial Dysfunction Signatures Associated with Ischemic Stroke
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Mitochondrial dysfunction contributes to the pathophysiology of ischemic stroke through impaired energy production, oxidative stress, and activation of cell death pathways. This study aimed to identify mitochondria-related transcriptomic signatures associated with ischemic stroke using an integrative bioinformatics approach. The GSE16561 peripheral whole-blood transcriptomic dataset, comprising 39 patients with ischemic stroke and 24 healthy controls, was analyzed to identify differentially expressed genes (DEGs). The identified DEGs were intersected with the MitoCarta3.0 mitochondrial gene set to identify mitochondria-related DEGs. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed to characterize the biological functions and pathways associated with these genes. A protein–protein interaction (PPI) network was subsequently constructed to identify highly connected hub genes. A total of 1,284 DEGs were identified, including 731 upregulated and 553 downregulated genes. Intersection with the MitoCarta3.0 gene set yielded 86 mitochondria-related DEGs, comprising 49 upregulated and 37 downregulated genes. Functional enrichment analyses revealed significant involvement of pathways and biological processes associated with oxidative phosphorylation, mitochondrial respiratory chain activity, ATP metabolism, reactive oxygen species (ROS) metabolism, mitochondrial organization, and apoptotic signaling. PPI network analysis identified NDUFA1, NDUFS2, UQCRC1, COX5A, and ATP5F1A as five major hub genes, suggesting coordinated transcriptional alterations across multiple components of the mitochondrial oxidative phosphorylation system. Overall, ischemic stroke was associated with a distinct mitochondria-related transcriptomic signature characterized primarily by alterations in mitochondrial energy metabolism and respiratory chain function. The identified hub genes represent potential molecular candidates for further investigation into the role of mitochondrial dysfunction in ischemic stroke. However, independent clinical and experimental validation is necessary to establish their biological relevance and potential translational significance.
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