Recent insights into the structure and function of Mitofusins in mitochondrial fusion

F1000Res. 2018 Dec 28:7:F1000 Faculty Rev-1983. doi: 10.12688/f1000research.16629.1. eCollection 2018.

Abstract

Mitochondria undergo frequent fusion and fission events to adapt their morphology to cellular needs. Homotypic docking and fusion of outer mitochondrial membranes are controlled by Mitofusins, a set of large membrane-anchored GTPase proteins belonging to the dynamin superfamily. Mitofusins include, in addition to their GTPase and transmembrane domains, two heptad repeat domains, HR1 and HR2. All four regions are crucial for Mitofusin function, but their precise contribution to mitochondrial docking and fusion events has remained elusive until very recently. In this commentary, we first give an overview of the established strategies employed by various protein machineries distinct from Mitofusins to mediate membrane fusion. We then present recent structure-function data on Mitofusins that provide important novel insights into their mode of action in mitochondrial fusion.

Keywords: Amphipathic Helix; Atlastin; Coiled-coil; Fusion; GTPase; Hemagglutinin; Heptad Repeat; Lipids; Membrane; Mitochondria; Mitofusin; SNARE.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • GTP Phosphohydrolases* / chemistry
  • GTP Phosphohydrolases* / physiology
  • Humans
  • Membrane Fusion
  • Mitochondrial Dynamics*
  • Mitochondrial Membrane Transport Proteins* / chemistry
  • Mitochondrial Membrane Transport Proteins* / physiology
  • Mitochondrial Membranes / metabolism

Substances

  • Mitochondrial Membrane Transport Proteins
  • GTP Phosphohydrolases
  • Mfn1 protein, human

Grants and funding

Research in the Cohen laboratory is supported by the Labex DYNAMO (ANR-11-LABX-0011-DYNAMO) and the ANR grant MOMIT (ANR-17-CE13-0026-01). The work of David Tareste is supported by the “Agence Nationale de la Recherche” (ANR-09-JCJC-0062-01), the “Association Française contre les Myopathies” (AFM Trampoline grant 16799 and AFM Research grant 20123), the “Fondation pour la Recherche Médicale” (FRM), and funds by the Labex “Who am I?”.