Mfn2
Domain
A helix bundle is formed by helices from the N-terminal and the C-terminal part of the protein. The GTPase domain cannot be expressed by itself, without the helix bundle. Rearrangement of the helix bundle and/or of the coiled coil domains may bring membranes from adjacent mitochondria into close contact, and thereby play a role in mitochondrial fusion.
Function
Mitochondrial outer membrane GTPase that mediates mitochondrial clustering and fusion (PubMed:12589796, PubMed:12598526, PubMed:14561718, PubMed:15322553). Mitochondria are highly dynamic organelles, and their morphology is determined by the equilibrium between mitochondrial fusion and fission events. Overexpression induces the formation of mitochondrial networks. Membrane clustering requires GTPase activity and may involve a major rearrangement of the coiled coil domains (By similarity). Plays a central role in mitochondrial metabolism and may be associated with obesity and/or apoptosis processes (PubMed:12598526). Plays an important role in the regulation of vascular smooth muscle cell proliferation (PubMed:15322553). Involved in the clearance of damaged mitochondria via selective autophagy (mitophagy). Is required for PRKN recruitment to dysfunctional mitochondria (By similarity). Involved in the control of unfolded protein response (UPR) upon ER stress including activation of apoptosis and autophagy during ER stress (By similarity). Acts as an upstream regulator of EIF2AK3 and suppresses EIF2AK3 activation under basal conditions (By similarity).
Post-translational modifications
Phosphorylated by PINK1.
Ubiquitinated by non-degradative ubiquitin by PRKN, promoting mitochondrial fusion; deubiquitination by USP30 inhibits mitochondrial fusion (By similarity). Ubiquitinated by HUWE1 when dietary stearate (C18:0) levels are low; ubiquitination inhibits mitochondrial fusion (By similarity).
Sequence Similarities
Belongs to the TRAFAC class dynamin-like GTPase superfamily. Dynamin/Fzo/YdjA family. Mitofusin subfamily.
Tissue Specificity
Ubiquitous. In brain, it is more expressed than MFN1, while it is expressed at a weaker level than MFN1 in heart and testis. Expressed at high level in elongating spermatids of seminiferous tubules. Expression is markedly down-regulated in highly proliferative vascular smooth muscle cells (VSMCs) from the genetic hypertensive animal model SHR, as well as in balloon-injured Wistar Kyoto arteries.
Cellular localization
- Mitochondrion outer membrane
- Multi-pass membrane protein
- Colocalizes with BAX during apoptosis.
Alternative names
Fzo1a, Mfn2, Mitofusin-2, Mitochondrial transmembrane GTPase FZO1A, Transmembrane GTPase MFN2, Protein HSG