Disease relevance of Mfn2

• However, in this experimental setting, hypertension-related left ventricular hypertrophy seemed to depend on blood pressure elevation rather than on the expression of AT1 receptors in the heart [1].

High impact information on Mfn2

• However, whereas Mfn2 mutant embryos have a specific and severe disruption of the placental trophoblast giant cell layer, Mfn1-deficient giant cells are normal [2].
• Similar to other efforts to understand complex, non-Mendelian phenotypes, genetic dissection of hypertension-related traits employs genomewide linkage analyses of families and association studies of patient cohorts, to uncover rare and common disease alleles, respectively [3].
• A genetic analysis proved that OPA1 was unable to tubulate and fuse mitochondria lacking the outer membrane mitofusin 1 but not mitofusin 2 [4].
• PGC-1alpha also stimulated the activity of the Mfn2 promoter, which required the integrity of estrogen-related receptor-alpha (ERRalpha)-binding elements located at -413/-398 [5].
• ERRalpha also activated the transcriptional activity of the Mfn2 promoter, and the effects were synergic with those of PGC-1alpha [5].

Biological context of Mfn2

• In contrast, cells lacking both Mfn1 and Mfn2 completely lacked mitochondrial fusion and showed severe cellular defects, including poor cell growth, widespread heterogeneity of mitochondrial membrane potential, and decreased cellular respiration [6].
• Here, we show that Mfn2 gene expression is induced in skeletal muscle and brown adipose tissue by conditions associated with enhanced energy expenditure, such as cold exposure or beta(3)-adrenergic agonist treatment [5].
• Exposure to cold substantially increased Mfn2 gene expression in skeletal muscle from heterozygous Mfn2 knock-out mice, which occurred in the presence of higher levels of PGC-1alpha mRNA compared with control mice [5].

Anatomical context of Mfn2

• In keeping with the role of peroxisome proliferator-activated receptor-gamma coactivator (PGC)-1alpha on energy expenditure, we demonstrate a stimulatory effect of PGC-1alpha on Mfn2 mRNA and protein expression in muscle cells [5].
• Evidence for a Mitochondrial Regulatory Pathway Defined by Peroxisome Proliferator-Activated Receptor-{gamma} Coactivator-1{alpha}, Estrogen-Related Receptor-{alpha}, and Mitofusin 2 [5].
• The role of hypertension-related gene in aortic vascular smooth muscle cells from mice and rats [7].

Associations of Mfn2 with chemical compounds

• Hypertension-related dopamine receptor changes were also investigated primarily in the kidney [8].

Other interactions of Mfn2

• Mfn2 loss of function reduced the stimulatory effect of PGC-1alpha on mitochondrial membrane potential [5].
• Our results indicate the existence of a regulatory pathway involving PGC-1alpha, ERRalpha, and Mfn2 [5].

References