MYG1 regulated metabolic reprogramming in acute myocardial infarction based on the AMPK/mTOR pathway

Objective This study aimed to investigate the role and regulatory mechanism of melanocyte proliferation gene 1 (MYG1) in metabolic reprogramming of cardiomyocytes in an acute myocardial infarction (AMI) model, and to determine whether MYG1 affected cardiac metabolism, autophagy, and cell survival through the AMPK/mTOR signaling pathway. Methods An in vivo rat AMI model was established, and MYG1 gene knockdown was achieved via intramyocardial injection of lentivirus. TTC staining, Western blot, immunohistochemistry, and TUNEL staining were used to evaluate the effects of MYG1 on myocardial infarct size, apoptosis, and metabolic enzyme expression. An in vitro oxygen-glucose deprivation (OGD) model was constructed using H9C2 cardiomyocytes. MYG1 was overexpressed and treated in combination with the glycolysis inhibitor 2-DG, AMPK activator AICAR, and mTOR inhibitor Rapamycin. Immunofluorescence, RT-qPCR, and transmission electron microscopy were used to assess changes in metabolic status, inflammatory cytokine levels, and mitochondrial function. Results MYG1 expression was significantly upregulated in myocardial tissues of AMI rats. MYG1 knockout reduced cardiomyocyte apoptosis, increased the expression of autophagy-related proteins PINK1 and Parkin, decreased levels of key glycolytic enzymes HK2 and ENO1, and promoted mitochondrial oxidative phosphorylation activity. In the in vitro OGD model, MYG1 overexpression promoted glycolysis and exacerbated OGD-induced cellular injury, whereas this effect was abolished by the glycolytic inhibitor 2-DG. Furthermore, the AMPK activator AICAR and the mTOR inhibitor Rapamycin enhanced the MYG1-mediated effects, as evidenced by increased oxygen consumption rate, decreased extracellular acidification rate, and improved mitochondrial autophagy and ultrastructural repair. Conclusion MYG1 promoted metabolic reprogramming of cardiomyocytes in acute myocardial infarction by regulating the AMPK/mTOR pathway. It enhanced glycolysis, suppressed mitochondrial function and autophagy, and participated in ischemic injury and repair. MYG1 may serve as a potential therapeutic target for AMI.