SLC25A23 depletion induces apoptosis through mitochondrial dysfunction in hepatocytes

Abstract

Mitochondrial carrier family (also known as solute carrier family 25, SLC25) facilitate the transportation of various nutrients across the mitochondrial inner membrane which includes amino acids, carboxylic acids, fatty acids, cofactors, inorganic ions, and nucleotides that are necessary for energy conversion and maintenance of cellular homeostasis. Solute Carrier Family 25 Member 23 (SLC25A23) is a mitochondrial Ca2+ dependent solute carrier protein. Mitochondrial dysfunction mediated ROS accumulation impairs fat homeostasis in the liver which leads to a pernicious cycle that aggravates the evolution of liver diseases including Nonalcoholic fatty liver disease (NAFLD) and (NASH). Various studies have been reported the hepatocyte-apoptosis mechanism on the NAFLD/NASH progression, however the molecular mechanism of mitochondria mediated apoptosis in hepatocytes are still not fully elucidated. In this study, we demonstrated that SLC25A23 depletion induced apoptosis through caspase-3 activation, increased Bax/Bcl-2 ratio, and ROS generation with SOD2 reduction in AML12 cells. In addition, SLC25A23 depletion impaired mitochondria dynamics through inhibition of Drp1 (Ser616) phosphorylation which led to mitochondrial dysfunction. Taken together, our study suggests the role of SLC25A23 alleviating apoptosis and mitochondrial dysfunction and might provide an ideal candidate for treatment of liver diseases.