Sam50 functions in mitochondrial intermembrane space bridging and biogenesis of respiratory complexes

Mol Cell Biol. 2012 Mar;32(6):1173-88. doi: 10.1128/MCB.06388-11. Epub 2012 Jan 17.


Mitochondria possess an outer membrane (OMM) and an inner membrane (IMM), which folds into invaginations called cristae. Lipid composition, membrane potential, and proteins in the IMM influence organization of cristae. Here we show an essential role of the OMM protein Sam50 in the maintenance of the structure of cristae. Sam50 is a part of the sorting and assembly machinery (SAM) necessary for the assembly of β-barrel proteins in the OMM. We provide evidence that the SAM components exist in a large protein complex together with the IMM proteins mitofilin and CHCHD3, which we term the mitochondrial intermembrane space bridging (MIB) complex. Interactions between OMM and IMM components of the MIB complex are crucial for the preservation of cristae. After destabilization of the MIB complex, we observed deficiency in the assembly of respiratory chain complexes. Long-term depletion of Sam50 influences the amounts of proteins from all large respiratory complexes that contain mitochondrially encoded subunits, pointing to a connection between the structural integrity of cristae, assembly of respiratory complexes, and/or the maintenance of mitochondrial DNA (mtDNA).

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Respiration
  • Gene Knockdown Techniques
  • HeLa Cells
  • Humans
  • Membrane Proteins / genetics
  • Membrane Proteins / metabolism*
  • Mitochondria / metabolism*
  • Mitochondria / ultrastructure*
  • Mitochondrial Proteins / genetics
  • Mitochondrial Proteins / metabolism*
  • Muscle Proteins / metabolism
  • Proteins / metabolism


  • CHCHD3 protein, human
  • IMMT protein, human
  • MTX1 protein, human
  • Membrane Proteins
  • Mitochondrial Proteins
  • Muscle Proteins
  • Proteins
  • SAMM50 protein, human