Mief2-KO Mouse

MIEF2, also known as mitochondrial elongation factor 2 or MiD49, is a mitochondrial outer membrane protein that functions as a key regulator of mitochondrial fission [1,3,4,6,7,8]. It is involved in various cellular processes, including metabolism, redox homeostasis, and apoptosis, and has been associated with multiple diseases, such as ovarian cancer, breast cancer, colorectal cancer, and doxorubicin-induced cardiotoxicity [1,2,3,5,6].

In ovarian cancer, MIEF2 promotes lipid synthesis by up-regulating SREBP1 and SREBP2 and their target genes, driving cancer progression through the ROS/AKT/mTOR signaling pathway [1]. In breast cancer, a soft extracellular matrix increases MIEF1/2-dependent mitochondrial fission, leading to redox homeostasis and chemotherapy resistance [2]. In colorectal cancer, low MIEF2 expression enhances oxaliplatin resistance by inhibiting the mitochondrial apoptosis pathway [5]. In cardiomyocytes, Foxo3a targets and suppresses MIEF2, inhibiting mitochondrial fission and protecting against doxorubicin-induced cardiotoxicity [6].

In conclusion, MIEF2 plays a crucial role in mitochondrial fission and is involved in multiple biological processes related to various diseases. Loss-of-function studies in different cell types and in vivo models have revealed its role in cancer progression and chemotherapy resistance, as well as in cardiotoxicity, providing potential therapeutic targets for these diseases.

References:

1. Zhao, Shuhua, Cheng, Lu, Shi, Yuan, Yun, Qinghui, Yang, Hong. 2021. MIEF2 reprograms lipid metabolism to drive progression of ovarian cancer through ROS/AKT/mTOR signaling pathway. In Cell death & disease, 12, 18. doi:10.1038/s41419-020-03336-6. https://pubmed.ncbi.nlm.nih.gov/33414447/

2. Romani, Patrizia, Nirchio, Nunzia, Arboit, Mattia, Martello, Graziano, Dupont, Sirio. 2022. Mitochondrial fission links ECM mechanotransduction to metabolic redox homeostasis and metastatic chemotherapy resistance. In Nature cell biology, 24, 168-180. doi:10.1038/s41556-022-00843-w. https://pubmed.ncbi.nlm.nih.gov/35165418/

3. Zhao, Shuhua, Zhang, Xiaohong, Shi, Yuan, Li, Jia, Yang, Hong. 2020. MIEF2 over-expression promotes tumor growth and metastasis through reprogramming of glucose metabolism in ovarian cancer. In Journal of experimental & clinical cancer research : CR, 39, 286. doi:10.1186/s13046-020-01802-9. https://pubmed.ncbi.nlm.nih.gov/33317572/

4. Xian, Hongxu, Liou, Yih-Cherng. 2019. Loss of MIEF1/MiD51 confers susceptibility to BAX-mediated cell death and PINK1-PRKN-dependent mitophagy. In Autophagy, 15, 2107-2125. doi:10.1080/15548627.2019.1596494. https://pubmed.ncbi.nlm.nih.gov/30894073/

5. Xie, Chaozheng, Li, Kang, Li, Ya, Wang, Wang, Wei, Zhengqiang. 2022. CRISPR-based knockout screening identifies the loss of MIEF2 to enhance oxaliplatin resistance in colorectal cancer through inhibiting the mitochondrial apoptosis pathway. In Frontiers in oncology, 12, 881487. doi:10.3389/fonc.2022.881487. https://pubmed.ncbi.nlm.nih.gov/36106106/

6. Zhou, Luyu, Li, Ruibei, Liu, Cuiyun, Zhao, Yanfang, Wang, Kun. 2017. Foxo3a inhibits mitochondrial fission and protects against doxorubicin-induced cardiotoxicity by suppressing MIEF2. In Free radical biology & medicine, 104, 360-370. doi:10.1016/j.freeradbiomed.2017.01.037. https://pubmed.ncbi.nlm.nih.gov/28137654/

7. Cheng, Zhiyong. . FoxO transcription factors in mitochondrial homeostasis. In The Biochemical journal, 479, 525-536. doi:10.1042/BCJ20210777. https://pubmed.ncbi.nlm.nih.gov/35195252/

8. Liu, Tong, Yu, Rong, Jin, Shao-Bo, Zhao, Jian, Nistér, Monica. 2013. The mitochondrial elongation factors MIEF1 and MIEF2 exert partially distinct functions in mitochondrial dynamics. In Experimental cell research, 319, 2893-904. doi:10.1016/j.yexcr.2013.07.010. https://pubmed.ncbi.nlm.nih.gov/23880462/