Conserved mechanism of Oxa1 insertion into the mitochondrial inner membrane

J Mol Biol. 2005 Dec 2;354(3):520-8. doi: 10.1016/j.jmb.2005.09.054. Epub 2005 Oct 5.


Oxa1 is the mitochondrial representative of a family of related proteins that mediate the insertion of substrate proteins into the membranes of bacteria, chloroplasts, and mitochondria. Several studies have demonstrated that the bacterial homologue YidC participates both in the direct uptake of proteins from the bacterial cytosol, and in the uptake of nascent proteins from the Sec translocase. Studies on the biogenesis of membrane proteins in mitochondria established that Oxa1 has the capability to receive substrates at the inner surface of the inner membrane. In this study, we asked if Oxa1 may similarly cooperate with a protein translocase within the membrane. Since Oxa1 is involved in its own biogenesis, we used the precursor of Oxa1 as a model protein and investigated its import pathway. We found that immediately after import into mitochondria, Oxa1 initially accumulates at Tim23 that forms the inner membrane protein translocase. Cleavage of the Oxa1 presequence is dependent on mtHsp70, a heat shock protein of the mitochondrial matrix. However, mutant mtHsp70 showing a defect in the release of bound substrate proteins does not interfere with subsequent membrane insertion, indicating that membrane insertion of the mature protein is essentially mtHsp70-independent. We conclude that Oxa1 has the ability to accept preproteins within the membrane.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Electron Transport Complex IV / genetics
  • Electron Transport Complex IV / metabolism*
  • HSP70 Heat-Shock Proteins / genetics
  • HSP70 Heat-Shock Proteins / metabolism
  • Intracellular Membranes / metabolism*
  • Membrane Transport Proteins / metabolism
  • Mitochondria / genetics
  • Mitochondria / metabolism*
  • Mitochondrial Proteins / genetics
  • Mitochondrial Proteins / metabolism*
  • Molecular Weight
  • Mutation / genetics
  • Nuclear Proteins / genetics
  • Nuclear Proteins / metabolism*
  • Protein Binding
  • Saccharomyces cerevisiae / genetics
  • Saccharomyces cerevisiae / metabolism
  • Saccharomyces cerevisiae Proteins / metabolism


  • HSP70 Heat-Shock Proteins
  • Membrane Transport Proteins
  • Mitochondrial Proteins
  • Nuclear Proteins
  • OXA1 protein
  • Saccharomyces cerevisiae Proteins
  • TIM23 protein, S cerevisiae
  • Electron Transport Complex IV