MARCHF5

Last update 08 May 2025

Basic Info

Synonyms

E3 ubiquitin-protein ligase MARCHF5, FLJ20445, MARCH-V

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Introduction

Mitochondrial E3 ubiquitin-protein ligase that plays a crucial role in the control of mitochondrial morphology by acting as a positive regulator of mitochondrial fission. May play a role in the prevention of cell senescence acting as a regulator of mitochondrial quality control. Promotes ubiquitination of FIS1, DNM1L and MFN1.

100 Clinical Results associated with MARCHF5

100 Translational Medicine associated with MARCHF5

0 Patents (Medical) associated with MARCHF5

132

Literatures (Medical) associated with MARCHF5

09 Apr 2025·mBio

E3 ubiquitin ligase MARCH5 positively regulates Japanese encephalitis virus infection by catalyzing the K27-linked polyubiquitination of viral E protein and inhibiting MAVS-mediated type I interferon production

Article

Author: Sun, Mingan ; Tang, Chenyang ; Shi, Jing ; Zhang, Linjie ; Li, Qingyu ; Li, Chenxi ; Liu, Ying ; Li, Yanhua ; Liu, Xiqian

ABSTRACT Membrane-associated RING-CH-type finger (MARCH) proteins, a class of E3 ubiquitin ligases, have been reported to be involved in the infection of multiple viruses and the regulation of type I interferon (IFN) production. However, the specific role and mechanisms by which MARCH proteins influence Japanese encephalitis virus (JEV) infection remain poorly understood. Here, we systematically investigate the functional relevance of MARCH proteins in JEV replication by examining the effects of siRNA-mediated knockdown of MARCHs on viral infection. We identified MARCH5 as a positive regulator of JEV replication. The knockout of MARCH5 dramatically reduced viral yields, whereas its overexpression significantly enhanced JEV replication. Mechanistically, MARCH5 specifically interacts with the JEV envelope (E) protein and promotes its K27-linked polyubiquitination at the lysine (K) residues 136 and 166. This ubiquitination enhances viral attachment to permissive cells. Substituting these lysine residues with arginine (R) attenuated JEV replication in vitro and reduced viral virulence in vivo . Furthermore, JEV infection upregulated the expression of MARCH5. We also discovered that MARCH5 degrades mitochondrial antiviral-signaling protein (MAVS) through the ubiquitin-proteasome pathway by catalyzing its K48-linked ubiquitination, thereby inhibiting type I IFN production in JEV-infected cells. This suppression of type I IFN further facilitates JEV infection. In conclusion, these findings disclosed a novel role of MARCH5 in positively regulating JEV infection and revealed an important mechanism employed by MARCH5 to regulate the innate immune response. IMPORTANCE JEV is the leading cause of viral encephalitis in many countries of Asia with an estimated 100,000 clinical human cases and causes economic loss to the swine industry. Until now, there is no clinically approved antiviral for the treatment of JEV infection. Although vaccination prophylaxis is widely regarded as the most effective strategy for preventing Japanese encephalitis (JE), the incidence of JE cases continues to rise. Thus, a deeper understanding of virus-host interaction will enrich our knowledge of the mechanisms underlying JEV infection and identify novel targets for the development of next-generation live-attenuated vaccines and antiviral therapies. To the best of our knowledge, this study is the first to identify MARCH5 as a pro-viral host factor that facilitates JEV infection. We elucidated two distinct mechanisms by which MARCH5 promotes JEV infection. First, MARCH5 interacts with viral E protein and mediates the K27-linked ubiquitination of E protein at the K136 and K166 residues to facilitate efficient viral attachment. Furthermore, double mutations of K136R-K166R attenuated JEV infection in vitro and reduced viral virulence in mice. Second, the upregulated expression of MARCH5 induced by JEV infection further suppresses the RIG-I-like receptor (RLR) signaling pathway to benefit viral infection. MARCH5 downregulates type I IFN production by conjugating the K48-linked polyubiquitin at the K286 of MAVS, which leads to MAVS degradation through the ubiquitin-proteasome pathway. In summary, this study provides novel insights into the role played by MARCH proteins in JEV infection and identifies specific ubiquitination sites on JEV E protein that could be targeted for viral attenuation and the development of antiviral therapeutics.

01 Apr 2025·Applied Biochemistry and Biotechnology

MARCH5 Promotes the Progression of Thyroid cancer by Regulating Mitochondrial Autophagy Protein FUNDC1-mediated Pyroptosis

Article

Author: Yang, Xiaozhou ; Yang, Huan ; Wang, Jiangang ; Yang, Xiaojun ; Ji, Guoxiong ; He, Xianli ; Tang, Haili ; Zhao, Huadong ; Chen, Xin

MARCH5 is a key regulatory factor in mitochondria. However, the expression and function of MARCH5 in thyroid cancer (TC) are not yet clear. The research explores the role and the potential mechanism of MARCH5 in the tumorigenesis of TC. MARCH5 expression were measured by qRT-PCR and Western blot. CCK-8 kits were used to measure the cell viability. Cell scratch assay and Tanswell assay were used to measure cell migration and invasion, respectively. The pyroptosis related proteins (NLRP3, caspase-1, GSDMD) and mitochondrial autophagy related proteins (LC3-II, p62, parkin, pink1) were detected. The mitochondrial ROS GSH, MDA, and SOD were detected using commercial kits. Finally, a TC mouse model was constructed to detect the role of MARCH5 in tumor growth in vivo. The results displayed that the expression of MARCH5 was increased in TC patients and cells, and was significantly correlated with prognosis. Functional studies have found that MARCH5 inhibits oxidative stress levels and mitochondrial autophagy in TPC-1 cells. Further research has found that MARCH5 promotes the progression of thyroid cancer by degrading FUNDC1 and inhibiting the mitochondrial autophagy mediated pyroptosis pathway, regulating cell proliferation, migration, and invasion in TPC-1 cells. More importantly, interference with MARCH5 inhibits tumor growth and further development of TC in vivo. In conclusion, MARCH5 promotes the progression of thyroid cancer by degrading FUNDC1 and inhibiting the mitochondrial autophagy mediated pyroptosis, regulating cell proliferation, migration, and invasion. This study provides new theoretical basis for the treatment and prevention of TC in clinical practice.

01 Mar 2025·Phytomedicine

Proteomic analysis reveals QiShenYiQi Pills ameliorates ischemia-induced heart failure through inhibition of mitochondrial fission

Article

Author: Zhang, Xinyao ; Yin, Xiaojian ; Hou, Liuqing ; Wang, Feizuo ; Zhang, Yajun ; Fan, Yuan-Ming ; Liu, Bo-Yu ; Li, Jia ; Li, Xiang ; Jia, Keke ; Tang, Zongxiang

BACKGROUNDQiShenYiQi Pills (QSYQ) has widely used in clinical treatment of cardiovascular diseases; however, the exact mechanism behind its effectiveness still requires further investigation.PURPOSEThe purpose of the study was to explore the potential mechanism of QSYQ in the treatment of ischemic heart failure from the perspective of proteomics.METHODSIn vivo, to observe QSYQ actions on the progression of ischemia-induced heart failure, cardiac function and remodeling was analyzed. The heart tissues of mice were used for Tandem Mass Tag (TMT)-based proteomic analysis. Cardiomyocytes were prepared and subjected to oxygen-glucose deprivation injury. QSYQ effects on differential proteins expressions, mitochondrial fission and mitochondrial function were assayed.RESULTSQSYQ treatment preserved cardiac function, limited cardiac fibrosis and alleviated cardiomyocyte hypertrophy in post-myocardial ischemia mice. Proteomic analysis revealed that QSYQ-responsive proteins were mainly involved in mitochondrial fission, including mitochondrial calcium uniporter (MCU), membrane associated ring-CH-type finger 5 (MARCHF5), and mitochondrial fission process 1 (MTFP1). Protein-protein interaction analysis revealed that MCU, MARCHF5 and MTFP1 commonly interacted with dynamin-related protein 1 (DRP1). Knockdown of MCU, MARCHF5, or MTFP1 attenuated excessive mitochondrial fission in cardiomyocytes through regulating DRP1 phosphorylation and its mitochondrial translocation. QSYQ decreased the phosphorylation of DRP1 at Ser616 and enhanced its inhibitory phosphorylation at Ser637, as well as mitigating the mitochondrial recruitment and oligomerization of DRP1, through downregulation of these three differential proteins. As a result, QSYQ alleviated aberrant mitochondrial fission, ameliorated mitochondrial dysfunction, and protected cardiomyocytes from ischemic injury.CONCLUSIONThe novelty lies in the proteomics-based investigation of the mechanism of QSYQ, uncovering that QSYQ mitigated ischemia-induced heart failure by suppressing MCU/MARCHF5/MTFP1-DRP1-driven mitochondrial fission.

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MARCHF5

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