Crucial Role Reported for TSPO in Viability and Steroidogenesis is a Misconception. Commentary: Conditional Steroidogenic Cell-Targeted Deletion of TSPO Unveils a Crucial role in Viability and Hormone-Dependent Steroid Formation

Recent reports on Leydig cell-specific Tspo conditional knockout Tspo(c Delta/Delta) mice (1), viable global Tspo knockout (Tspo(-/-)) mice from two independent laboratories (2, 3), and clones of CRISPR/Cas9-mediated Tspo-deleted MA-10 Leydig cells (MA-10Tsp(o Delta/Delta)) (4) established that TSPO is not essential for steroid hormone biosynthesis or viability [reviewed in Ref. (5, 6)]. These reports refuted 25 years of dogma that described TSPO as a mitochondrial cholesterol transport protein, indispensable for steroidogenesis. In response, the research group involved in most of the early studies linking TSPO and steroidogenesis investigated Leydig cell-specific and adrenocortical cell-specific Tspo(c Delta/Delta) mice (7) and presented results that seem to repudiate the recent findings and revive the old model. In this commentary, we would like to point out that interpretations made in the manuscript by Fan et al. (7) are seriously flawed.