Mitochondrial Dynamics Regulates Oxidative Metabolism in Leydig Tumor Cells

CECILIA PODEROSO; CRISTINA PAZ; KATIA E. HELFENBERGER; ERNESTO J. PODESTA

The Biochemistry of Oxidative Stress

Springer Nature

Lugar: New York; Año: 2016; p. 391 - 408

Steroidogenesis in Leydig cells is predominantly regulated by trophic hormone LH, whose signaling pathway involves PKA activation. PKA-mediated phosphorylation is involved in the induction and activation of steroidogenic acute regulatory (StAR) protein, which in turn activates the delivery of cholesterol from the outer to the inner mitochondrial membrane, the rate-limiting step in the biosynthesis of all steroid hormones. The access of cholesterol to the inner mitochondrial membrane allows its conversion to pregnenolone by cytochrome P450 side-chain cleavage enzyme. StAR-mediated access of cholesterol to the mitochondria and pregnenolone synthesis are common steps in the hormone-stimulated biosynthesis of steroid hormones. Mitochondria are cellular organelles with crucial roles including ATP synthesis, metabolic integration, ROS synthesis and apoptosis, all processes linked to steroidogenesis rates. Mitochondrial dynamics is then key to normal cell movement and function. In this context, this chapter focuses on reviewing the contribution of mitochondrial dynamics to Leydig cell function and metabolism, including efficient steroid production, and intends to highlight the mechanisms underlying mitochondrial changes and the correct localization of key mitochondrial proteins to achieve maximal steroidogenesis after hormone stimulation.