Peptide Targeting of Mitochondria Elicits Testosterone Formation

Abstract

Testosterone (T) is the principal sex hormone responsible for growth and development of the reproductive system in male vertebrates.1 It has historically received much attention not only from the medical and scientific communities2 but also from the general public, owing to its psychological and behavioral effects.3 T drives the asymmetry of several biological processes spanning virilization to anabolism, disease prevention,1 and aging.4 In this issue of Molecular Therapy, Aghazadeh et al.5 describe a novel fusion peptide, TVS167, that can induce T formation in rat testes and increase its serum level as well as rescue its synthesis in adult male rats exposed to antagonists of the gonadotropin-releasing hormone, which constitutes the initial step in the hypothalamic–pituitary–gonadal axis governing T production. This peptide acts by exploiting the interaction between the voltage-dependent anion channel 1 (VDAC1) and the 18-kDa translocator protein (TSPO) within the mitochondrial transduceosome, a multicomponent molecular machine that controls lipid import and steroidogenesis. This peptide reveals a regulatory mechanism in the mitochondrial pathway of steroid anabolism that could provide a new target for therapeutic intervention (see model in Figure 1).