MFN2
GeneName
MFN2
Summary
MFN2, also known as mitofusin 2 or Mfn-2, is an 86 kDa protein located primarily in the mitochondrial outer membrane and is also found in the cytosol and associated with the microtubule cytoskeleton. It plays a critical role in mitochondrial fusion and organisation, facilitating the merging of mitochondria to maintain their function and integrity. MFN2 is involved in various biological processes, including aerobic respiration, apoptotic processes, and the regulation of smooth muscle cell proliferation. Its GTPase activity and ability to bind to ubiquitin protein ligases suggest a role in mitochondrial dynamics and cellular signalling pathways.
Importance
MFN2 is relevant to: - Mitochondrial dynamics and health, with implications for metabolic diseases and neurodegenerative disorders due to its role in mitochondrial fusion. - Apoptosis and cellular stress responses, as it is involved in the regulation of cell death pathways. - Developmental biology, particularly in processes like blastocyst formation and camera-type eye morphogenesis. - Vascular biology, influencing smooth muscle cell behaviour and potentially contributing to vascular diseases.
Top Products
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Abcam Product Citation Summary
The data indicates a significant focus on the role of MFN2 in various contexts related to mitochondrial dynamics, fusion, and function across different species, particularly in mouse and human models. Studies often involve conditions such as myocardial infarction, high-fat diet responses, and mitochondrial protein expression, highlighting the importance of MFN2 in cellular health and disease mechanisms.
Abcam Product Citation Table
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:11181170, PubMed:11950885, PubMed:19889647, PubMed:26214738, PubMed:28114303). Mitochondria are highly dynamic organelles, and their morphology is determined by the equilibrium between mitochondrial fusion and fission events (PubMed:28114303). Overexpression induces the formation of mitochondrial networks (PubMed:28114303). Membrane clustering requires GTPase activity and may involve a major rearrangement of the coiled coil domains (Probable). Plays a central role in mitochondrial metabolism and may be associated with obesity and/or apoptosis processes (By similarity). Plays an important role in the regulation of vascular smooth muscle cell proliferation (By similarity). Involved in the clearance of damaged mitochondria via selective autophagy (mitophagy) (PubMed:23620051). Is required for PRKN recruitment to dysfunctional mitochondria (PubMed:23620051). 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).
Involvement in disease
Charcot-Marie-Tooth disease, axonal, 2A2B
CMT2A2B
An axonal form of Charcot-Marie-Tooth disease, a disorder of the peripheral nervous system, characterized by progressive weakness and atrophy, initially of the peroneal muscles and later of the distal muscles of the arms. Charcot-Marie-Tooth disease is classified in two main groups on the basis of electrophysiologic properties and histopathology: primary peripheral demyelinating neuropathies (designated CMT1 when they are dominantly inherited) and primary peripheral axonal neuropathies (CMT2). Neuropathies of the CMT2 group are characterized by signs of axonal degeneration in the absence of obvious myelin alterations, normal or slightly reduced nerve conduction velocities, and progressive distal muscle weakness and atrophy. CMT2A2B is a severe form with autosomal recessive inheritance.
None
The disease is caused by variants affecting the gene represented in this entry.
Charcot-Marie-Tooth disease, axonal, 2A2A
CMT2A2A
An autosomal dominant, axonal form of Charcot-Marie-Tooth disease, a disorder of the peripheral nervous system, characterized by progressive weakness and atrophy, initially of the peroneal muscles and later of the distal muscles of the arms. Charcot-Marie-Tooth disease is classified in two main groups on the basis of electrophysiologic properties and histopathology: primary peripheral demyelinating neuropathies (designated CMT1 when they are dominantly inherited) and primary peripheral axonal neuropathies (CMT2). Neuropathies of the CMT2 group are characterized by signs of axonal degeneration in the absence of obvious myelin alterations, normal or slightly reduced nerve conduction velocities, and progressive distal muscle weakness and atrophy.
None
The disease is caused by variants affecting the gene represented in this entry.
Neuropathy, hereditary motor and sensory, 6A, with optic atrophy
HMSN6A
An autosomal dominant neurologic disorder characterized by optic atrophy and peripheral sensorimotor neuropathy manifesting as axonal Charcot-Marie-Tooth disease. Charcot-Marie-Tooth disease is a disorder of the peripheral nervous system, characterized by progressive weakness and atrophy, initially of the peroneal muscles and later of the distal muscles of the arms. It is classified in two main groups on the basis of electrophysiologic properties and histopathology: primary peripheral demyelinating neuropathies and primary peripheral axonal neuropathies. Peripheral axonal neuropathies are characterized by signs of axonal regeneration in the absence of obvious myelin alterations, and normal or slightly reduced nerve conduction velocities.
None
The disease is caused by variants affecting the gene represented in this entry.
Lipomatosis, multiple symmetric, with or without peripheral neuropathy
MSL
An autosomal recessive disorder characterized by the growth of unencapsulated, lipomatous masses affecting the upper body, especially the cervical and thoracic regions. Lipomatosis can be disfiguring, and lipoma growth around the neck may cause difficulty swallowing or breathing. The age at onset ranges from childhood to young adulthood. Some patients develop distal muscle weakness and atrophy due to axonal peripheral neuropathy.
None
The disease is caused by variants affecting the gene represented in this entry.
Post-translational modifications
Phosphorylated by PINK1.
Ubiquitinated by non-degradative ubiquitin by PRKN, promoting mitochondrial fusion; deubiquitination by USP30 inhibits mitochondrial fusion (PubMed:23620051). Ubiquitinated by HUWE1 when dietary stearate (C18:0) levels are low; ubiquitination inhibits mitochondrial fusion (PubMed:26214738, PubMed:30217973).
Sequence Similarities
Belongs to the TRAFAC class dynamin-like GTPase superfamily. Dynamin/Fzo/YdjA family. Mitofusin subfamily.
Tissue Specificity
Ubiquitous; expressed at low level. Highly expressed in heart and kidney.
Cellular localization
- Mitochondrion outer membrane
- Multi-pass membrane protein
- Colocalizes with BAX during apoptosis.
Alternative names
CPRP1, KIAA0214, MFN2, Mitofusin-2, Transmembrane GTPase MFN2