Abstract P1158: Glucolipotoxicity Curtails Mitophagy In Cardiomyocytes

Abstract

Diabetic patients suffer from complications of hyperglycemia and hyperlipidemia, which can lead to cardiovascular problems. The precise mechanism behind this phenomenon is unclear, but it is often associated with cellular damage and metabolic dysfunction. Mitochondria are responsible for energy production within cells, and abnormal metabolic conditions like diabetes can cause mitochondrial dysfunction. Mitophagy, the selective lysosomal degradation of damaged mitochondria, is a critical process for maintaining mitochondrial quality. However, the effects of hyperglycemia and hyperlipidemia on mitophagy in cardiomyocytes are not well characterized. We hypothesized that mitophagy is compromised in cardiac muscle cells by hyperglycemic and hyperlipidemic stresses. In this study, we investigated the effects of high-glucose (HG) and high-fat (HF) conditions on mitophagy in cardiomyocytes. We cultured H9C2 cardiac cells in media containing high levels of glucose (30 mM) and/or palmitate (25uM). The mitochondrial fractions were collected and the mitophagy flux was measured. Western blot analysis showed that the protein levels of microtubule-associated protein light chain 3 form II (LC3-II), a marker of mitophagosome, were reduced by HG and/or HF in either the absence or the presence of lysosomal inhibitors, suggesting inhibited mitophagy flux. The mitophagy flux was also determined by using dual fluorescent reporter that express mitochondria-targeted RFP-GFP fusion protein. Future studies will determine if HG and HF induce diabetic cardiac injury via impaired mitophagy.