Two distinct and independent mitochondrial targeting signals function in the sorting of an inner membrane protein, cytochrome c1

Isabel Arnold*, Heike Fölsch, Walter Neupert, Rosemary A. Stuart

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

42 Scopus citations

Abstract

Proteins of the mitochondrial inner membrane display a wide variety of orientations, many spanning the membrane more than once. Some of these proteins are synthesized with NH2-terminal clearable targeting sequences (presequences) whereas others are targeted to mitechondria via internal signals. Here we report that two distinct mitochondrial targeting signals can be present in precursors of inner membrane proteins, an NH2-terminal one and a second, internal one. Using cytochrome c1 as a model protein, we demonstrate that these two mitochondrial targeting signals operate independently of each other. The internal targeting signal, consisting of a transmembrane segment and a stretch of positively charged amino acid residues directly following it, initially directs the translocation of the preprotein into the intermembrane space. It then inserts into the inner membrane from the intermembrane space side in a Δψ-dependent manner and thereby determines the orientation the protein attains in the inner membrane. Analysis of a number of other presequence-containing protein of the inner membrane suggest that they too contain such internal targeting signals.

Original languageEnglish (US)
Pages (from-to)1469-1476
Number of pages8
JournalJournal of Biological Chemistry
Volume273
Issue number3
DOIs
StatePublished - Jan 16 1998

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Fingerprint Dive into the research topics of 'Two distinct and independent mitochondrial targeting signals function in the sorting of an inner membrane protein, cytochrome c<sub>1</sub>'. Together they form a unique fingerprint.

Cite this