Abstract
INTRODUCTION: Mitochondrial dynamics play a vital role in maintaining cardiac energy balance and cellular homeostasis. Increasing evidence suggests that dysregulated mitochondrial dynamics contribute to the development of acute myocardial infarction (AMI). However, the underlying molecular mechanisms and related biomarkers remain largely unclear. METHODS: In this study, transcriptomic profiling of AMI and control samples was used to identify mitochondrial dynamics-associated genes (MD-RGs) linked to AMI progression. Based on the expression of 50 curated MD-RGs, AMI samples were classified into molecular subgroups using single-sample gene set enrichment analysis (ssGSEA). Differentially expressed genes were integrated into multiple machine learning models to identify potential diagnostic biomarkers. Expression validation and receiver operating characteristic (ROC) analyses were performed to assess diagnostic accuracy. Functional enrichment, immune infiltration, and N6-methyladenosine (m6A) regulator correlation analyses were conducted to explore biological mechanisms. Key cell types were identified through single-cell RNA sequencing (scRNA-seq) analysis, and biomarker expression was validated by reverse transcription quantitative PCR (RT-qPCR) in patient-derived samples. RESULTS: Two genes, COX7B and SNORD54, were identified as novel biomarkers associated with mitochondrial dynamics in AMI. ROC and nomogram analyses confirmed their strong diagnostic performance. Enrichment analysis revealed shared pathways including oxidative phosphorylation and Notch signaling, while six m6A regulators (HNRNPC, KIAA1429, METTL3, WTAP, YTHDC1, and YTHDC2) were markedly downregulated, suggesting possible epigenetic involvement. RT-qPCR confirmed reduced expression of COX7B and SNORD54 in AMI tissues. Single-cell analysis further identified monocytes and natural killer (NK) cells as key cell types linked to these biomarkers. DISCUSSION: Collectively, this study identifies COX7B and SNORD54 as mitochondrial dynamics-related biomarkers and highlights the role of monocytes and NK cells in AMI, offering new insight into mitochondrial dysfunction-driven cardiac injury and potential targets for precision diagnosis and therapy.