<p>The influence of circRNAs on the pathological process of acute myocardial infarction (AMI) has not been entirely clarified. This study was to systematically screen the aberrantly expressed circRNAs in AMI and to reveal the molecular mechanism of circPDXDC1 in AMI and its interactions with the RNA-binding protein ELAVL1.&#xa0;Based on the GSE160717 dataset (GEO database), differentially expressed circRNAs were screened using the Limma R package and visualized by volcano plots with heat maps. The stability of circPDXDC1 was verified by actinomycin D treatment, RNase R digestion, and divergent/convergent primer PCR. OGD-treated AC16 and HL-1 cell models and AMI mouse model were constructed. siRNA knockdown, overexpression vector transfection, and lentiviral intervention techniques were used to assess mitochondrial function and autophagy in combination with LDH/CK-MB assay, ROS/ATP/MMP analysis, MDC staining and Western blot. The interaction mechanism between circPDXDC1 and ELAVL1 was analyzed by RNA-pull down, RIP, FISH, and ubiquitination experiments.&#xa0;Bioinformatics analysis identified circPDXDC1 (hsa_circ_0038011) to be significantly highly expressed in myocardial tissues of AMI patients and models, with a high stability to actinomycin D and RNase R. circPDXDC1 downregulation significantly ameliorated OGD-induced cellular injury, as evidenced by reduced LDH/CK-MB release, decreased ROS/MDA levels, ATP/MMP restoration, and reversal of autophagy marker (ATG5/Beclin-1/p62). circPDXDC1 bound to ELAVL1 and promoted its ubiquitinated degradation, while ELAVL1 overexpression antagonized OGD-induced mitochondrial dysfunction and autophagy hyperactivation. circPDXDC1 knockdown significantly attenuated AMI in mice by upregulating ELAVL1. CircPDXDC1 exacerbates mitochondrial dysfunction and autophagy dysregulation by targeting the ELAVL1 ubiquitination degradation.</p>