Melanocyte proliferation gene 1 regulated metabolic reprogramming in acute myocardial infarction based on the AMPK/mTOR pathway.

Abstract

Melanocyte proliferation gene 1 (MYG1) has been implicated in cellular metabolic regulation; however, its role in cardiomyocyte metabolic reprogramming during acute myocardial infarction (AMI) remains unclear. In this study, a rat AMI model was established, and MYG1 knockdown was achieved by lentiviral injection to investigate its effects on myocardial injury and metabolism. Myocardial infarct size, apoptosis, and the expression of metabolic- and autophagy-related proteins were assessed using TTC staining, Western blotting, immunohistochemistry, and TUNEL assays. In parallel, an oxygen-glucose deprivation (OGD) model was generated in H9C2 cells, in which MYG1 was overexpressed alone or in combination with the glycolysis inhibitor 2-deoxy-d-glucose (2-DG), the AMPK activator AICAR, or the mTOR inhibitor rapamycin. MYG1 expression was significantly upregulated in myocardial tissues following AMI. MYG1 knockdown attenuated cardiomyocyte apoptosis, enhanced the expression of mitophagy-related proteins PINK1 and Parkin, reduced the levels of key glycolytic enzymes hexokinase 2 and enolase 1, and promoted mitochondrial oxidative phosphorylation. In vitro, MYG1 overexpression facilitated glycolysis and aggravated OGD-induced cellular injury, whereas inhibition of glycolysis by 2-DG effectively reversed these effects. Furthermore, modulation of the AMPK/mTOR pathway influenced MYG1-associated metabolic alterations, as evidenced by changes in cellular metabolic flux and improved mitochondrial autophagy and ultrastructural integrity. These findings suggest that MYG1 participates in cardiomyocyte metabolic reprogramming during AMI, potentially through regulation of the AMPK/mTOR pathway, and may represent a candidate target for therapeutic intervention.