High impact information on MFN1

• Importantly, NO-induced neuronal cell death was mitigated by Mfn1 and Drp1(K38A) [1].
• The nucleotide sequence alignment also indicated that the cDNA FLJ20693 and the cDNA for 741-residue human mitofusin 1 (TG741) possibly resulted from the event of alternative splicing from which a 127-bp region was retained in the latter [2].
• Mitochondrial fusion in higher eukaryotes requires at least two essential GTPases, Mitofusin 1 and Mitofusin 2 (Mfn2) [3].
• This process, but not Mfn1 targeting, was dependent on the inner membrane potential, indicating that overexpressed Mfn1 stimulates fusion [4].
• To examine the function of Mfn proteins, tethering of mitochondrial membranes was measured in vitro by fluorescence microscopy using green fluorescence protein- or red fluorescent protein-tagged and Mfn1-expressing mitochondria, or by immunoprecipitation using mitochondria harboring HA- or FLAG-tagged Mfn proteins [5].

Biological context of MFN1

• The mitofusins (Mfn1 and Mfn2) are homologs of the Drosophila protein fuzzy onion (Fzo) that associate with mitochondria and alter mitochondrial morphology when expressed by transient transfection in tissue culture cells [6].
• Mitofusin (Mfn) proteins regulate the biogenesis and maintenance of the mitochondrial network, and when inactivated, cause a failure in the mitochondrial architecture and decreases in oxidative capacity and glucose oxidation [7].
• On the outer membrane, the fuzzy onions/mitofusin proteins form complexes in trans that mediate homotypic physical interactions between adjacent mitochondria and are likely directly involved in outer membrane fusion [8].
• Conversely, a protein variant carrying a point mutation in the G2 motif of the Mfn1 GTPase domain acted as a dominant negative: overexpression of Mfn1T109A resulted in fragmentation of mitochondria [9].
• In addition, recent reports shed new light on the physiological importance of Mitofusin function suggesting a role in mitochondrial metabolism, apoptosis as well as cellular signalling [10].

Anatomical context of MFN1

• Forced expression of Mfn1 in cultured cells caused formation of characteristic networks of mitochondria [9].
• The approximately 450 kDa complex contained oligomerized Mfn1 from distinct apposing membranes (docking complex), whereas the approximately 250 kDa complex was composed of Mfn1 present on the same membrane or in the membrane-solubilized state (cis complex) [5].
• What is the biological significance of the two mitofusin proteins present in the outer mitochondrial membrane of mammalian cells [11]?
• The hfzo genes were expressed mainly in the brain and in muscle that are postmitotic, but not in the pancreas [12].

Associations of MFN1 with chemical compounds

• Sucrose density gradient centrifugation followed by co-immunoprecipitation revealed that Mfn1 produced oligomerized approximately 250 kDa and approximately 450 kDa complexes in a GTP-dependent manner [5].

Other interactions of MFN1

• In younger cells, mitochondria were more mobile, were shorter, occupied a smaller percentage of neuronal processes, and expressed greater mitofusin-1 and lower dynamin-related protein-1 protein levels compared with older cells [13].

Analytical, diagnostic and therapeutic context of MFN1

• Two human Fzo-homologs, mitofusins Mfn1 and Mfn2, are shown by RT-PCR and western blot to be ubiquitous mitochondrial proteins [14].

References