Dissecting membrane insertion of mitochondrial beta-barrel proteins

Cell. 2008 Mar 21;132(6):1011-24. doi: 10.1016/j.cell.2008.01.028.


Communication of mitochondria with the rest of the cell requires beta-barrel proteins of the outer membrane. All beta-barrel proteins are synthesized as precursors in the cytosol and imported into mitochondria by the general translocase TOM and the sorting machinery SAM. The SAM complex contains two proteins essential for cell viability, the channel-forming Sam50 and Sam35. We have identified the sorting signal of mitochondrial beta-barrel proteins that is universal in all eukaryotic kingdoms. The beta-signal initiates precursor insertion into a hydrophilic, proteinaceous membrane environment by forming a ternary complex with Sam35 and Sam50. Sam35 recognizes the beta-signal, inducing a major conductance increase of the Sam50 channel. Subsequent precursor release from SAM is coupled to integration into the lipid phase. We propose that a two-stage mechanism of signal-driven insertion into a membrane protein complex and subsequent integration into the lipid phase may represent a general mechanism for biogenesis of beta-barrel proteins.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Membrane Transport Proteins / chemistry
  • Membrane Transport Proteins / metabolism
  • Mitochondria / metabolism
  • Mitochondrial Membrane Transport Proteins
  • Mitochondrial Membranes / chemistry
  • Mitochondrial Membranes / metabolism*
  • Mitochondrial Proteins / chemistry
  • Mitochondrial Proteins / metabolism*
  • Protein Sorting Signals
  • Protein Structure, Secondary
  • Protein Structure, Tertiary
  • Protein Transport
  • Saccharomyces cerevisiae / cytology
  • Saccharomyces cerevisiae / metabolism
  • Saccharomyces cerevisiae Proteins / chemistry
  • Saccharomyces cerevisiae Proteins / metabolism


  • Membrane Transport Proteins
  • Mitochondrial Membrane Transport Proteins
  • Mitochondrial Proteins
  • Protein Sorting Signals
  • Saccharomyces cerevisiae Proteins
  • Sam35 protein, S cerevisiae
  • Sam50 protein, S cerevisiae
  • Tom40 protein, S cerevisiae