Fig. 2

A Brief Schematic Diagram of Testosterone Synthesis in Leydig Cells. LH binds to receptors on LCs, triggering steroidogenesis. Cholesterol is transported from the OMM to the IMM via the transduceosome, a complex that includes StAR, TSPO, and VDAC1. StAR facilitates cholesterol translocation across the mitochondrial membrane. TSPO, with a high affinity for cholesterol, plays a central role in this process. The 14–3-3γ and 14–3-3ε adaptor proteins, part of the transduceosome, act as negative regulators. Specifically, 14–3-3ε impairs the interaction between TSPO and VDAC1, slowing cholesterol entry into mitochondria. Once inside the IMM, cholesterol is converted by Cyp11a1 into pregnenolone, which is then metabolized into testosterone by 3β-HSD. LCs, Leydig cells; LH, luteinizing hormone; OMM, outer mitochondrial membrane; IMM, inner mitochondrial membrane; StAR, steroidogenic acute regulatory protein; TSPO, translocator protein; VDAC1, voltage-dependent anion channel 1; Created in BioRender.com