C- to N-terminal translocation of preproteins into mitochondria

Heike Fölsch, Brigitte Gaume, Michael Brunner, Walter Neupert, Rosemary A. Stuart*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

37 Scopus citations


Nuclear-encoded mitochondrial matrix proteins in most cases contain N-terminal targeting signals and are imported in a linear N- to C-terminal (N→C) fashion. We asked whether import can also occur in a C- to N-terminal direction (C→N). We placed targeting signal at the C-terminus of passenger proteins. Import did occur in this 'backwards' fashion. It paralleled that of the 'normal' N→C mechanism in terms of efficiency, rate, energetic requirements and ability to mediate unfolding and refolding during and following import of protein containing a folded domain. Furthermore, this reaction was mediated by the TIM17-23 machinery. The import pathway taken by certain inner-membrane proteins contains elements of such a C→N translocation pathway, as they are targeted to mitochondria by internal targeting signals. These internal targeting signals appear to form loop structures together with neighbouring transmembrane segments, and penetrate the inner membrane in a membrane-potential-dependent manner. The dimeric TIM17-23 complex, together with mt-Hsp70, acts on both sides of the loop structure to facilitate their translocation into the matrix. On one side of the loop import occurs in the common N→C direction, whereas the translocation of the other side involves the novel C→N import direction. We conclude therefore that the mitochondrial import machinery displays no preference for the directionality of the import process.

Original languageEnglish (US)
Pages (from-to)6508-6515
Number of pages8
JournalEMBO Journal
Issue number22
StatePublished - Nov 16 1998


  • Mitochondria
  • Protein import
  • Reverse translocation
  • Yeast

ASJC Scopus subject areas

  • Neuroscience(all)
  • Molecular Biology
  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)

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