ClpX, a component of the ClpXP proteolytic complex, is an AAA+ ATPase unfoldase. In bacteria, it couples with ClpP protease for regulated proteolysis, recognizing specific residues in substrates and facilitating their degradation, thus playing a crucial role in protein quality control and homeostasis, modulating various biological processes such as virulence expression, competence development [2]. In mitochondria, it functions as a peptidase, activating the mitochondrial unfolded protein response to maintain protein homeostasis [1].

Two conditional knockout (cKO) mouse models demonstrated that ClpX deficiency impairs mitochondrial functions and quantity in spermatocytes, affecting energy supply during meiosis, attenuating zygotene-pachytene transformation, and leading to apoptosis of dysregulated spermatocytes, ultimately decreasing testicular size. It was also found that the mTORC1 pathway was over-activated after ClpX deletion in spermatocytes, and long-term in vivo inhibition of mTORC1 signaling via rapamycin treatment partially rescued spermatogenesis, revealing the critical role of ClpX in regulating meiosis and spermatogenesis [1].

In conclusion, ClpX is essential for maintaining protein homeostasis both in bacteria and mitochondria. In mice, cKO models have shown its significance in spermatogenesis, where it impacts mitochondrial functions and mTORC1 signaling. Understanding ClpX's function through these models provides insights into male infertility and related reproductive disorders.