Coassembly of Mgm1 isoforms requires cardiolipin and mediates mitochondrial inner membrane fusion.
Two dynamin-related protein (DRP) families are essential for fusion of the outer and inner mitochondrial membranes, Fzo1 (yeast)/Mfn1/Mfn2 (mammals) and Mgm1 (yeast)/Opa1 (mammals), respectively. Fzo1/Mfns possess two medial transmembrane domains, which place their critical GTPase and coiled-coil domains in the cytosol. In contrast, Mgm1/Opa1 are present in cells as long (l) isoforms that are anchored via the N terminus to the inner membrane, and short (s) isoforms were predicted to be soluble in the intermembrane space. We addressed the roles of Mgm1 isoforms and how DRPs function in membrane fusion. Our analysis indicates that in the absence of a membrane, l- and s-Mgm1 both exist as inactive GTPase monomers, but that together in trans they form a functional dimer in a cardiolipin-dependent manner that is the building block for higher-order assemblies.
DeVay
Rachel M
RM
Department of Molecular and Cellular Biology, University of California, Davis, Davis, CA 95616, USA.
Dominguez-Ramirez
Lenin
L
Lackner
Laura L
LL
Hoppins
Suzanne
S
Stahlberg
Henning
H
Nunnari
Jodi
J
D002308:Cardiolipins / Q000378:metabolism*; D019204:GTP-Binding Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D015966:Gene Expression Regulation, Fungal; D006160:Guanosine Triphosphate / Q000378:metabolism; D006868:Hydrolysis; D007700:Kinetics; D008081:Liposomes; D008561:Membrane Fusion; D008928:Mitochondria / Q000378:metabolism*; D051336:Mitochondrial Membranes / Q000378:metabolism*; D024101:Mitochondrial Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D008958:Models, Molecular; D009154:Mutation; D011487:Protein Conformation; D020033:Protein Isoforms; D055503:Protein Multimerization; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000254:growth & development / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D013329:Structure-Activity Relationship
D002308:Cardiolipins; D008081:Liposomes; C082883:MGM1 protein, S cerevisiae; D024101:Mitochondrial Proteins; D020033:Protein Isoforms; D011993:Recombinant Fusion Proteins; D029701:Saccharomyces cerevisiae Proteins; D006160:Guanosine Triphosphate; D019204:GTP-Binding Proteins