Journal
EMBO REPORTS
Volume 19, Issue 6, Pages -Publisher
WILEY
DOI: 10.15252/embr.201643637
Keywords
amphipathic helix; fusion; membrane; mitochondria; Mitofusin
Categories
Funding
- Agence Nationale de la Recherche [ANR-09-JCJC-0062-01]
- Association Francaise contre les Myopathies (AFM Trampoline grant) [16799]
- Association Francaise contre les Myopathies (AFM Research grant) [20123]
- Fondation pour la Recherche Medicale (FRM)
- Who am I? Labex
- Paris Descartes University
- FRM
- PhD Program Frontieres du Vivant (FdV)-Cursus Bettencourt
- Centre National de la Recherche Scientifique (CNRS)
- France BioImaging infrastructures [ANR-10-INBS-04]
- Commissariat General a l'Investissement (CGI)
Ask authors/readers for more resources
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 GTPase domain, a first heptad repeat domain (HR1), two transmembrane domains, and a second heptad repeat domain (HR2). 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 insitu and invitro fusion assays, we show that HR1 induces membrane fusion and possesses a conserved amphipathic helix that folds upon interaction with the lipid bilayer surface. Our results strongly suggest that HR1 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.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available