The Mitochondrial Inner.2FOuter Membrane Fusion .28MMF.29 Family Mitochondrial fusion

1 mitochondrial inner/outer membrane fusion (mmf) family

1.1 family members
1.2 mitofusins: mfn1 , mfn2
1.3 yeast mitochondrial fusion proteins

the mitochondrial inner/outer membrane fusion (mmf) family

the mitochondrial inner/outer membrane fusion (mmf) family (tc# 9.b.25) family of proteins play role in mitochondrial fusion events. family belongs larger mitochondrial carrier (mc) superfamily. dynamic nature of mitochondria critical function. chen , chan (2010) have discussed molecular basis of mitochondrial fusion, protective role in neurodegeneration, , importance in cellular function. mammalian mitofusins mfn1 , mfn2, gtpases localized outer membrane, mediate outer-membrane fusion. opa1, gtpase associated inner membrane, mediates subsequent inner-membrane fusion. mutations in mfn2 or opa1 cause neurodegenerative diseases. mitochondrial fusion enables content mixing within mitochondrial population, thereby preventing permanent loss of essential components. cells reduced mitochondrial fusion show subpopulation of mitochondria lack mtdna nucleoids. such mtdna defects lead respiration-deficient mitochondria, , accumulation in neurons leads impaired outgrowth of cellular processes , consequent neurodegeneration.

family members

a representative list of proteins belonging mmf family available in transporter classification database.

9.b.25.1.1 - mitochondrial inner/outer membrane fusion complex, fzo/mgm1/ugo1. ugo1 protein member of mc superfamily.
9.b.25.2.1 - mammalian mitochondrial membrane fusion complex, mitofusin 1 (mfn1)/mfn2/optical atrophy protein 1 (opa1) complex. subfamily includes mitofusins 1 , 2.

mitofusins: mfn1 , mfn2

mfn1 , mfn2 (tc# 9.b.25.2.1; q8iwa4 , o95140, respectively), in mammalian cells required mitochondrial fusion, mfn1 , mfn2 possess functional distinctions. instance, formation of tethered structures in vitro occurs more readily when mitochondria isolated cells overexpressing mfn1 mfn2. in addition, mfn2 has been shown associate bax , bak (bcl-2 family, tc#1.a.21), resulting in altered mfn2 activity, indicating mitofusins possess unique functional characteristics. lipidic holes may open on opposing bilayers intermediates, , fusion in cardiac myocytes coupled outer mitochondrial membrane destabilization opportunistically employed during mitochondrial permeability transition.

mutations in mfn2 (but not mfn1) result in neurological disorder charcot-marie-tooth syndrome. these mutations can complemented formation of mfn1–mfn2 hetero-oligomers not homo-oligomers of mfn2–mfn2. suggests within mfn1–mfn2 hetero-oligomeric complex, each molecule functionally distinct. suggests control of expression levels of each protein represents basic form of regulation alter mitochondrial dynamics in mammalian tissues. indeed, expression levels of mfn1 , mfn2 vary according cell or tissue type mitochondrial morphology.

yeast mitochondrial fusion proteins

in yeast, 3 proteins essential mitochondrial fusion. fzo1 (p38297) , mgm1 (p32266) conserved guanosine triphosphatases reside in outer , inner membranes, respectively. @ each membrane, these conserved proteins required distinct steps of membrane tethering , lipid mixing. third essential component ugo1, outer membrane protein region homologous distantly related region in mitochondrial carrier (mc) family. hoppins et al., 2009 showed ugo1 modified member of family, containing 3 transmembrane domains , existing dimer, structure critical fusion function of ugo1. analyses of ugo1 indicate required both outer , inner membrane fusion after membrane tethering, indicating operates @ lipid-mixing step of fusion. role distinct fusion dynamin-related proteins , demonstrates @ each membrane, single fusion protein not sufficient drive lipid-mixing step. instead, step requires more complex assembly of proteins. formation of fusion pore has not yet been demonstrated. ugo1 protein member of mc superfamily.