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 do...

Full description

Saved in:
Bibliographic Details
Published in:The Journal of cell biology 2009-09, Vol.186 (6), p.793-803
Main Authors: DeVay, Rachel M, Dominguez-Ramirez, Lenin, Lackner, Laura L, Hoppins, Suzanne, Stahlberg, Henning, Nunnari, Jodi
Format: Article
Language:English
Subjects:
Biochemistry
Cardiolipins - metabolism
Cells
Gene Expression Regulation, Fungal
GTP-Binding Proteins - chemistry
GTP-Binding Proteins - genetics
GTP-Binding Proteins - metabolism
Guanosine Triphosphate - metabolism
Hydrolysis
Kinetics
Liposomes
Membrane Fusion
Membranes
Mitochondria - metabolism
Mitochondrial Membranes - metabolism
Mitochondrial Proteins - chemistry
Mitochondrial Proteins - genetics
Mitochondrial Proteins - metabolism
Models, Molecular
Mutation
Protein Conformation
Protein Isoforms
Protein Multimerization
Proteins
Recombinant Fusion Proteins - metabolism
Saccharomyces cerevisiae - genetics
Saccharomyces cerevisiae - growth & development
Saccharomyces cerevisiae - metabolism
Saccharomyces cerevisiae Proteins - chemistry
Saccharomyces cerevisiae Proteins - genetics
Saccharomyces cerevisiae Proteins - metabolism
Structure-Activity Relationship
Yeast
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary: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.
ISSN:0021-9525
1540-8140
DOI:10.1083/jcb.200906098