MIEF2 (mitochondrial
elongation factor 2) is one of the key regulators of mitochondrial fission. Bioinformatics analysis indicated that high expression of MIEF2 predicted a poor prognosis in
ovarian cancer patients. However, the relationship between MIEF2 and aberrant lipid metabolism in OC remains elusive. In this study, we demonstrated that MIEF2 significantly promoted
lipid synthesis, while has no significant effect on
fatty acid uptake and oxidation in OC cells. MIEF2 enhanced de novo
fatty acid synthesis through up-regulating the expression of
sterol regulatory element binding protein 1 (SREBP1) and its transcriptional target lipogenic genes ACC1, FASN and SCD1. Meanwhile, MIEF2-promoted
cholesterol biosynthesis through up-regulating the expression of
sterol regulatory element binding protein 2 (SREBP2) and its transcriptional target
cholesterol biosynthesis genes HMGCS1 and HMGCR. Mechanistically, increased mitochondrial
reactive oxygen species (ROS) production and subsequently activation of AKT/mTOR signaling pathway was found to be involved in the up-regulation of SREBP1 and SREBP2 in OC cells. Moreover, cell growth and
metastasis assays indicated that MIEF2-regulated
fatty acid synthesis and
cholesterol biosynthesis played a critical role in the progression of OC. Taken together, our findings indicate that MIEF2 is a critical regulator of
lipid synthesis in OC, which provides a strong line of evidence for this molecule to serve as a drug target in the treatment of this
malignancy.