Mitochondria are dynamic organelles that are important for cell growth and proliferation. Dysregulated mitochondrial dynamics are highly associated with the initiation and progression of various cancers, including ovarian cancer. However, the regulatory mechanism underlying mitochondrial dynamics is still not fully understood. Previously, our study showed that carnitine palmitoyltransferase 1A (CPT1A) is highly expressed in ovarian cancer cells and promotes the development of ovarian cancer. Here, we find that CPT1A regulates mitochondrial dynamics and promotes mitochondrial fission in ovarian cancer cells. Our study futher shows that CPT1A regulates mitochondrial fission and function through mitochondrial fission factor (MFF) to promote the growth and proliferation of ovarian cancer cells. Mechanistically, we show that CPT1A promotes succinylation of MFF at lysine 302 (K302), which protects against Parkin-mediated ubiquitin-proteasomal degradation of MFF. Finally, the study shows that MFF is highly expressed in ovarian cancer cells and that high MFF expression is associated with poor prognosis in patients with ovarian cancer. MFF inhibition significantly inhibits the progression of ovarian cancer in vivo. Overall, CPT1A regulates mitochondrial dynamics through MFF succinylation to promote the development of ovarian cancer. Moreover, our findings suggest that MFF is a potential therapeutic target for ovarian cancer.

线粒体是动态细胞器，对细胞生长和增殖很重要。线粒体动力学失调与各种癌症（包括卵巢癌）的发生和进展密切相关。然而，线粒体动力学的调控机制仍不完全清楚。此前，我们的研究表明，肉毒碱棕榈酰转移酶1A（CPT1A）在卵巢癌细胞中高表达，并促进卵巢癌的发生发展。在这里，我们发现 CPT1A 调节卵巢癌细胞中的线粒体动力学并促进线粒体裂变。我们的研究进一步表明，CPT1A通过线粒体裂变因子（MFF）调节线粒体裂变和功能，促进卵巢癌细胞的生长和增殖。从机制上讲，我们发现 CPT1A 促进 MFF 在赖氨酸 302 (K302) 处的琥珀酰化，从而防止 Parkin 介导的 MFF 泛素蛋白酶体降解。最后，研究表明MFF在卵巢癌细胞中高表达，并且MFF高表达与卵巢癌患者的不良预后相关。MFF 抑制显着抑制体内卵巢癌的进展。总体而言，CPT1A通过MFF琥珀酰化调节线粒体动力学，促进卵巢癌的发展。此外，我们的研究结果表明 MFF 是卵巢癌的潜在治疗靶点。