OPA1 controls apoptotic cristae remodeling independently from mitochondrial fusion

Cell. 2006 Jul 14;126(1):177-89. doi: 10.1016/j.cell.2006.06.025.

Abstract

Mitochondria amplify activation of caspases during apoptosis by releasing cytochrome c and other cofactors. This is accompanied by fragmentation of the organelle and remodeling of the cristae. Here we provide evidence that Optic Atrophy 1 (OPA1), a profusion dynamin-related protein of the inner mitochondrial membrane mutated in dominant optic atrophy, protects from apoptosis by preventing cytochrome c release independently from mitochondrial fusion. OPA1 does not interfere with activation of the mitochondrial "gatekeepers" BAX and BAK, but it controls the shape of mitochondrial cristae, keeping their junctions tight during apoptosis. Tightness of cristae junctions correlates with oligomerization of two forms of OPA1, a soluble, intermembrane space and an integral inner membrane one. The proapoptotic BCL-2 family member BID, which widens cristae junctions, also disrupts OPA1 oligomers. Thus, OPA1 has genetically and molecularly distinct functions in mitochondrial fusion and in cristae remodeling during apoptosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis / genetics*
  • Cell Line
  • GTP Phosphohydrolases / genetics
  • GTP Phosphohydrolases / metabolism*
  • Membrane Fusion / physiology*
  • Mice
  • Mice, Knockout
  • Mitochondria / genetics
  • Mitochondria / metabolism*
  • Mitochondria / ultrastructure
  • Mitochondrial Membranes / metabolism*
  • Mitochondrial Membranes / ultrastructure
  • Proto-Oncogene Proteins c-bcl-2 / metabolism
  • Signal Transduction / physiology
  • Tight Junctions / metabolism
  • Tight Junctions / ultrastructure
  • bcl-2 Homologous Antagonist-Killer Protein / metabolism
  • bcl-2-Associated X Protein / metabolism

Substances

  • Proto-Oncogene Proteins c-bcl-2
  • bcl-2 Homologous Antagonist-Killer Protein
  • bcl-2-Associated X Protein
  • GTP Phosphohydrolases
  • Opa1 protein (GTPase), mouse