OPA1 silencing in AC16: a model to study MAO A upregulation and autophagy dysregulation

Heart failure and cardiovascular disease are becoming a worldwide health crisis, they are often characterized by profound alterations in cardiomyocyte function and energy metabolism, in this context mitochondrial dysfunction plays a crucial role. Cellular quality control mechanisms such as autophagy and its selective form, mitophagy, have important functions in maintaining homeostasis and degrading damaged organelles. Monoamine oxidase A is one of the primary sources of oxidative stress in the mitochondria, being responsible for the deamination of neurotransmitters such as norepinephrine and serotonin, it generates reactive oxygen species. These toxic byproducts in the heart could be one of the causes of mitochondrial dysfunction, affecting the myocardium and leading to cardiovascular disease. OPA1 is a protein involved in mitochondrial fusion and cristae remodelling, which regulates mitochondrial dynamics. Previous studies from a murine model with cardiac downregulation of OPA1 was characterized by an impairment in autophagy, it also exhibited a marked upregulation of MAO A. The objective of the study was to generate a cellular model characterized by OPA1 downregulation that could be used to investigate the possible relationship between MAO A, OPA1 and autophagy in cardiomyocytes. The model was generated employing a human cardiomyocyte cell line AC16 derived from the adult ventricular tissue and it confirmed the same MAO A upregulation as the previous murine model.