Binding of a specific ligand inhibits import of a purified precursor protein into mitochondria

Nature. 1986 Jul 17-23;322(6076):228-32. doi: 10.1038/322228a0.


Methotrexate, a folate antagonist, blocks import into mitochondria of mouse dihydrofolate reductase fused to a mitochondrial presequence. Methotrexate does not mask the presequence, but stabilizes the dihydrofolate reductase moiety. It does not inhibit import of the authentic precursor from which the presequence is derived. This suggests that dihydrofolate reductase must at least partly unfold in order to be transported across mitochondrial membranes.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Biological Transport / drug effects
  • Electron Transport Complex IV / metabolism
  • Escherichia coli / metabolism
  • Fungal Proteins / metabolism
  • Methotrexate / pharmacology*
  • Mice
  • Mitochondria / metabolism*
  • Protein Conformation
  • Protein Precursors / metabolism*
  • Protein Processing, Post-Translational / drug effects*
  • Recombinant Proteins / metabolism*
  • Saccharomyces cerevisiae / metabolism
  • Tetrahydrofolate Dehydrogenase / metabolism


  • Fungal Proteins
  • Protein Precursors
  • Recombinant Proteins
  • Tetrahydrofolate Dehydrogenase
  • Electron Transport Complex IV
  • Methotrexate