Connection of the mitochondrial outer and inner membranes by Fzo1 is critical for organellar fusion

J Cell Biol. 2001 Feb 19;152(4):683-92. doi: 10.1083/jcb.152.4.683.

Abstract

Mitochondrial membrane fusion is a process essential for the maintenance of the structural integrity of the organelle. Since mitochondria are bounded by a double membrane, they face the challenge of fusing four membranes in a coordinated manner. We provide evidence that this is achieved by coupling of the mitochondrial outer and inner membranes by the mitochondrial fusion machinery. Fzo1, the first known mediator of mitochondrial fusion, spans the outer membrane twice, exposing a short loop to the intermembrane space. The presence of the intermembrane space segment is required for the localization of Fzo1 in sites of tight contact between the mitochondrial outer and inner membranes. Mutations in the intermembrane space domain of yeast Fzo1 relieve the association with the inner membrane. This results in a loss of function of the protein in vivo. We propose that the mitochondrial fusion machinery forms membrane contact sites that mediate mitochondrial fusion. A fusion machinery that is in contact with both mitochondrial membranes appears to be functionally important for coordinated fusion of four mitochondrial membranes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Polarity
  • Cytosol
  • Fungal Proteins / genetics
  • Fungal Proteins / metabolism
  • GTP Phosphohydrolases / genetics
  • GTP Phosphohydrolases / metabolism*
  • Intracellular Membranes / physiology*
  • Membrane Fusion*
  • Membrane Proteins / genetics
  • Membrane Proteins / metabolism*
  • Mitochondria / physiology*
  • Mitochondrial Proteins
  • Models, Biological
  • Mutation
  • Protein Transport
  • Recombinant Fusion Proteins / metabolism
  • Saccharomyces cerevisiae Proteins
  • Submitochondrial Particles
  • Yeasts

Substances

  • Fungal Proteins
  • Membrane Proteins
  • Mitochondrial Proteins
  • Recombinant Fusion Proteins
  • Saccharomyces cerevisiae Proteins
  • FZO1 protein, S cerevisiae
  • GTP Phosphohydrolases