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The heptad repeat domain 1 of Mitofusin has membrane destabilization function in mitochondrial fusion
Author(s) -
Daste Frédéric,
Sauvanet Cécile,
Bavdek Andrej,
Baye James,
Pierre Fabienne,
Le Borgne Rémi,
David Claudine,
Rojo Manuel,
Fuchs Patrick,
Tareste David
Publication year - 2018
Publication title -
embo reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.584
H-Index - 184
eISSN - 1469-3178
pISSN - 1469-221X
DOI - 10.15252/embr.201643637
Subject(s) - heptad repeat , lipid bilayer fusion , snap25 , mfn2 , microbiology and biotechnology , biology , biophysics , mitochondrial fusion , lipid bilayer , inner mitochondrial membrane , mitochondrial membrane transport protein , transmembrane domain , translocase of the outer membrane , translocase of the inner membrane , mitochondrion , chemistry , membrane , biochemistry , peptide sequence , vesicle , synaptic vesicle , gene , mitochondrial dna
Mitochondria are double‐membrane‐bound organelles that constantly change shape through membrane fusion and fission. Outer mitochondrial membrane fusion is controlled by Mitofusin, whose molecular architecture consists of an N‐terminal GTP ase domain, a first heptad repeat domain ( HR 1), two transmembrane domains, and a second heptad repeat domain ( HR 2). The mode of action of Mitofusin and the specific roles played by each of these functional domains in mitochondrial fusion are not fully understood. Here, using a combination of in situ and in vitro fusion assays, we show that HR 1 induces membrane fusion and possesses a conserved amphipathic helix that folds upon interaction with the lipid bilayer surface. Our results strongly suggest that HR 1 facilitates membrane fusion by destabilizing the lipid bilayer structure, notably in membrane regions presenting lipid packing defects. This mechanism for fusion is thus distinct from that described for the heptad repeat domains of SNARE and viral proteins, which assemble as membrane‐bridging complexes, triggering close membrane apposition and fusion, and is more closely related to that of the C‐terminal amphipathic tail of the Atlastin protein.