Role of Constitutive STAR in Mitochondrial Structure and Function in MA-10 Leydig Cells

Abstract

The steroidogenic acute regulatory protein (STAR; STARD1) is critical for the transport of cholesterol into the mitochondria for hormone-induced steroidogenesis. Steroidogenic cells express STAR under control conditions (constitutive STAR). On hormonal stimulation, STAR localizes to the outer mitochondrial membrane (OMM) where it facilitates cholesterol transport and where it is processed to its mature form. Here, we show that knockout of Star in MA-10 mouse tumor Leydig cells (STARKO1) causes defects in mitochondrial structure and function under basal conditions. We also show that overexpression of Star in STARKO1 cells exacerbates, rather than recovers, mitochondrial structure and function, which further disrupts the processing of STAR at the OMM. Our findings suggest that constitutive STAR is necessary for proper mitochondrial structure and function and that mitochondrial dysfunction leads to defective STAR processing at the OMM.