Carnitine palmitoyltransferase 1A promotes mitochondrial fission by enhancing MFF succinylation in ovarian cancer

Mitochondria are dynamic organelles and 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 unclear and needs to be further studied. 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 found that CPT1A regulates mitochondrial dynamics and promotes mitochondrial fission in ovarian cancer cells. Further study showed that CPT1A regulates mitochondrial fission and function through MFF to promote the growth and proliferation of ovarian cancer cells. Mechanistically, CPT1A promotes succinylation of MFF at lysine 302 (K302), which protects against Parkin-mediated ubiquitin-proteasomal degradation of MFF. Finally, the study showed that MFF was highly expressed in ovarian cancer cells and that high MFF expression is associated with poor prognosis in patients with ovarian cancer. MFF inhibition significantly inhibited the progression of ovarian cancer in vivo. Together, CPT1A regulates mitochondrial dynamics through MFF succinylation to promote the development of ovarian cancer. And MFF is a potential therapeutic target for ovarian cancer.