The mitofusin 2 (MFN2) gene encodes a critical mitochondrial outer membrane protein that plays a pivotal role in mitochondrial fusion, a process essential for maintaining mitochondrial morphology, function, and cellular energy homeostasis. MFN2 is a dynamin-like GTPase that facilitates the tethering and fusion of mitochondria, enabling the exchange of contents such as DNA, proteins, and metabolites between organelles. Beyond its role in mitochondrial dynamics, MFN2 is implicated in regulating mitochondrial-ER contacts, apoptosis, and cellular metabolism. Mutations in the MFN2 gene are associated with Charcot-Marie-Tooth disease type 2A (CMT2A), a hereditary neuropathy characterized by axonal degeneration. Additionally, dysregulation of MFN2 has been linked to metabolic disorders, cardiovascular diseases, and cancer. Given its central role in mitochondrial health, MFN2 is a promising therapeutic target for diseases involving mitochondrial dysfunction.
Human MFN2 adenoviral particles are genetically engineered viral vectors designed to deliver the MFN2 gene to mammalian cells for research or therapeutic purposes. These particles are based on a replication-defective adenovirus and can efficiently transduce a variety of cell types, including primary and dividing cells. Researchers use them to overexpress MFN2 in cell lines or animal models to study its effects on mitochondrial fusion, apoptosis, or metabolic pathways. In translational research, MFN2 adenoviral vectors have the potential to be used in gene therapy approaches for mitochondrial diseases, neurodegenerative diseases, or metabolic syndrome.
Mitochondrial dynamics plays a crucial role in mitochondrial function. The mitofusin 2 (MFN2) gene encodes a mitochondrial membrane protein that participates in mitochondrial fusion to maintain and operate the mitochondrial network. In addition, MFN2 is essential for mitophagy. Here, researchers investigated the role of MFN2 in mitochondrial fusion and mitophagy in angiotensin II-stimulated cardiomyocyte injury. The study showed that MFN2 expression gradually decreased with angiotensin II stimulation. MFN2 deficiency impaired mitochondrial quality, leading to aggravated angiotensin II-induced mitochondrial damage. MFN2 overexpression alleviated angiotensin II-induced ROS generation and increased apoptosis rate. In addition, MFN2 alleviated angiotensin II-induced MMP reduction. MFN2 promoted mitochondrial fusion, and MFN2 promoted Parkin translocation and phosphorylation, leading to mitophagy. The effects of MFN2 overexpression could be reversed by autophagy inhibitors.
To evaluate the effect of MFN2 overexpression on Ang II-induced cardiomyocyte injury, the researchers analyzed intracellular ROS generation, MMP, and apoptosis rate. Cardiomyocytes were divided into four groups: (1) Control+Ad-Control, cells were transfected with control adenovirus and not treated with Ang II; (2) Control+Ad-MFN2, cells were transfected with MFN2 adenovirus and not treated with Ang II; (3) Ang II+Ad-Control, cells were transfected with control adenovirus and treated with 1 μM Ang II for 24 h; (4) Ang II+Ad-MFN2, cells were transfected with MFN2 adenovirus and treated with 1 μM Ang II for 24 h. Compared with the Ang II+Ad-Control group, the ROS production in the Ang II+Ad-MFN2 group was significantly reduced (Figure 1A). In addition, after transfection with adenovirus overexpressing MFN2, JC-1 staining showed that overexpression of MFN2 alleviated the decrease of MMP caused by Ang II (Figure 1B). The decrease of MMP represents the early stage of apoptosis. In addition, TUNEL assay showed that overexpression of MFN2 significantly reduced AngII-induced cardiomyocyte apoptosis (Figure 1C). These results indicate that overexpression of MFN2 can prevent Ang II-induced damage, including oxidative stress, MMP, and cell apoptosis rate.
Figure 1. Overexpression of MFN2 prevented Ang II-induced cardiomyocyte injury. (Xiong W, et al., 2019)
Customer Reviews
Reliable adenoviral particles
The Human MFN2 adenoviral particles exceeded our expectations. The viral prep was clean, and the gene expression was robust—great for mitochondrial research!
United Kingdom
02/07/2023
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