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.

MIEF2（线粒体伸长因子2）是线粒体裂变的关键调节因子之一。生物信息学分析表明，MIEF2的高表达预示卵巢癌患者预后不良。然而，MIEF2 与 OC 中异常脂质代谢之间的关系仍然难以捉摸。在这项研究中，我们证明MIEF2显着促进脂质合成，而对OC细胞中脂肪酸的摄取和氧化没有显着影响。 MIEF2 通过上调甾醇调节元件结合蛋白 1 (SREBP1) 及其转录靶脂肪生成基因 ACC1、FASN 和 SCD1 的表达来增强脂肪酸从头合成。同时，MIEF2通过上调甾醇调节元件结合蛋白2（SREBP2）及其转录靶胆固醇生物合成基因HMGCS1和HMGCR的表达来促进胆固醇生物合成。从机制上讲，线粒体活性氧 (ROS) 产生的增加以及随后 AKT/mTOR 信号通路的激活被发现与 OC 细胞中 SREBP1 和 SREBP2 的上调有关。此外，细胞生长和转移测定表明 MIEF2 调节的脂肪酸合成和胆固醇生物合成在 OC 的进展中发挥着关键作用。总而言之，我们的研究结果表明 MIEF2 是 OC 中脂质合成的关键调节因子，这为该分子作为治疗这种恶性肿瘤的药物靶点提供了强有力的证据。