1.N.6.1.2
The mammalian mitochondrial membrane fusion complex, Mitofusin 1/2 (Mfn1)/Mfn2/Optical Atrophy Protein 1 (OPA1) complex (the equivalent of the yeast Ugo1 protein)/dynamin-related protein 1 Drp1 (Chandhok et al. 2018). Mfn1 and Mfn2 are two very similar (60% identity) GTPase dynamin-like proteins in the outer mitochondrial membrane (members of the CDD P-loop[ NTPase Family) while OPA1 is a sequence divergent GTPase in the inner membrane (Chen and Chan, 2010).  Mfn2 plays roles in mitochondrial fusion and mitochondrial endoplasmic reticulum interactions (Ranieri et al. 2013; Schneeberger et al. 2013). Mfn2, when defective can give rise to Charcot-Marie-Tooth disease, diabetes, neurodegenerative diseases, obesity and vascular diseases (Chandhok et al. 2018).  It may also function in  insulin-dependent myogenesis (Pawlikowska et al. 2007). Drp1 (DLP1, DNM1L) mediates membrane fusion and fission through oligomerization into membrane-associated tubular structures that wrap around the scission site to constrict and sever the mitochondrial membrane in a GTP hydrolysis-dependent mechanism (Smirnova et al. 2001; Taguchi et al. 2007). Sequences flanking the TMSs facilitate membrane fusion by mitofusin (Huang et al. 2017). Opa1 is a mitochondrial remodeling protein with a dual role in maintaining mitochondrial morphology and energetics by mediating inner membrane fusion and maintaining the cristae structure. This and the fusion/fission process by dynamins is described by Lee and Yoon 2018. MFN2 deficiency affects calcium homeostasis in lung adenocarcinoma cells via downregulation of UCP4 (Zhang et al. 2023).  Inhibition of MFN1 restores tamoxifen-induced apoptosis in resistant cells by disrupting aberrant mitochondrial fusion dynamics (Song et al. 2024). Mfn2 regulates calcium homeostasis and suppresses PASMCs proliferation via interaction with IP3R3 to mitigate pulmonary arterial hypertension (Wang et al. 2025).