Fig. 9: A schematic representation of the proposed model illustrating the role of ClpP/ClpX in spermatogenesis.

ClpP/ClpX deficiency impairs mitochondrial functions and leads to reduced mitochondrial quality in spermatocytes. This deficiency disrupts energy supply during meiosis and attenuates the zygotene-pachytene transformation of spermatocytes. Consequently, dysregulated spermatocytes undergo apoptosis, resulting in decreased testicular size and the formation of vacuolar structures within the seminiferous tubules. Furthermore, the deletion of ClpP/ClpX leads to the over-activation of the mTORC1 pathway in spermatocytes. Long-term inhibition of the mTORC1 signaling, achieved through rapamycin treatment in vivo, partially rescues spermatogenesis. Overall, this model highlights the crucial roles of ClpP and ClpX in regulating mitochondrial functions, meiosis, and spermatogenesis.