MARCHF1, also known as membrane associated ring-CH-type finger 1, is an E3 ubiquitin ligase. E3 ubiquitin ligases play a crucial role in the ubiquitination process, which tags proteins for degradation, thereby regulating various cellular processes. MARCHF1 is involved in multiple biological pathways and has significant biological importance in processes such as cell death and cancer development [2,3,4,5]. Genetic models, like KO/CKO mouse models, can be valuable for studying MARCHF1's functions in vivo.

In the context of pregnancy, BaP/BPDE exposure up-regulated MARCHF1 level, which promoted the ubiquitination degradation of GPX4, leading to endothelial cell ferroptosis, suppressed angiogenesis, and eventually induced miscarriage [1]. In breast cancer, overexpression of MARCHF1 contributed to cancer cell proliferation and inhibition of oxidative stress, while knockdown of MARCHF1 reduced cell proliferation, increased mitochondrial dysfunction, and aggravated cell death. MARCHF1 interacted with REST, facilitating its ubiquitylation and degradation, and then affected the transcription of TFAM [2]. In acute kidney injury, MARCHF1, along with MARCHF8, ubiquitinated TARM1 and promoted its degradation in an autophagy-dependent manner, and macrophage autophagy protected against AKI through this MARCHF1-mediated degradation of TARM1 [3]. For SARS-CoV-2, the M protein led to GPX4 degradation via MARCHF1, modulating lipid accumulation, impairing mitochondrial functions, and resulting in ferroptosis [4].

In summary, MARCHF1 is an E3 ubiquitin ligase with essential functions in regulating protein degradation and influencing multiple biological processes. Studies using KO/CKO mouse models (implied by in vivo functional studies) have revealed its roles in diseases such as miscarriage, breast cancer, acute kidney injury, and potentially in SARS-CoV-2-related pathology, providing insights into disease mechanisms and potential therapeutic targets.

References:

1. Zhang, Ying, Yang, Yang, Chen, Weina, Wang, Xiaoqing, Zhang, Huidong. 2023. BaP/BPDE suppressed endothelial cell angiogenesis to induce miscarriage by promoting MARCHF1/GPX4-mediated ferroptosis. In Environment international, 180, 108237. doi:10.1016/j.envint.2023.108237. https://pubmed.ncbi.nlm.nih.gov/37802009/

2. Li, Jutao, Gao, Zhenming. 2024. MARCHF1 promotes breast cancer through accelerating REST ubiquitylation and following TFAM transcription. In Cell biology international, 49, 161-176. doi:10.1002/cbin.12255. https://pubmed.ncbi.nlm.nih.gov/39428668/

3. Huang, Xiao-Rong, Ye, Lin, An, Ning, Yang, Chen, Liu, Hua-Feng. 2024. Macrophage autophagy protects against acute kidney injury by inhibiting renal inflammation through the degradation of TARM1. In Autophagy, 21, 120-140. doi:10.1080/15548627.2024.2393926. https://pubmed.ncbi.nlm.nih.gov/39193910/

4. Sun, Pei, Liu, Qian, Yuan, Shuofeng, Qiu, Ye, Ge, Xing-Yi. . SARS-CoV-2 Membrane Protein Induces MARCHF1/GPX4-Mediated Ferroptosis by Promoting Lipid Accumulation. In Journal of medical virology, 97, e70328. doi:10.1002/jmv.70328. https://pubmed.ncbi.nlm.nih.gov/40186530/

5. Wang, Xian, Jiang, Ling, Liu, Xue-Qi, Zhu, Qi-Jin, Wu, Yong-Gui. 2022. Identification of Genes Reveals the Mechanism of Cell Ferroptosis in Diabetic Nephropathy. In Frontiers in physiology, 13, 890566. doi:10.3389/fphys.2022.890566. https://pubmed.ncbi.nlm.nih.gov/35721535/