MRPL13 enhances mitochondrial function and promotes tumor progression in ovarian cancer by inhibiting mPTP opening via SLC25A6.

Tumor cells typically exhibit dysregulation of mitochondrial energy metabolism and cell death. The role of mitochondrial function in ovarian cancer (OC) progression has garnered substantial attention, yet its precise molecular mechanisms remain elusive. Mitochondrial ribosomal protein L13 (MRPL13), involved in the translation of oxidative phosphorylation (OXPHOS) complex subunits, plays a critical role in regulating mitochondrial function. Our study demonstrated that MRPL13 is highly expressed in OC tissues and correlated with poor prognosis. Both in vitro and in vivo experiments confirmed that MRPL13 overexpression significantly promotes the malignant biological behavior of OC, while MRPL13 knockdown induces the opposite phenotype. Moreover, MRPL13 knockdown impairs mitochondrial function in OC cells, leading to decreased OXPHOS and ATP levels, increased reactive oxygen species (ROS) generation, mitochondrial depolarization, aberrant opening of the mitochondrial permeability transition pore (mPTP), and mitochondrial structural damage. Mechanistically, MRPL13 specifically interacts with SLC25A6 and facilitates its degradation via lysine (K)48-linked ubiquitination. MRPL13 inhibits mPTP opening by accelerating the degradation of SLC25A6, thereby preventing cytochrome c release into the cytoplasm, inhibiting cell death, and enhancing mitochondrial function. In conclusion, our study elucidates the mechanism by which the MRPL13-SLC25A6 axis enhances mitochondrial function and promotes tumor progression in OC by inhibiting mPTP opening, suggesting that MRPL13 holds significant potential for prognostic evaluation and targeted therapy in OC.