Adriamycin, a drug interacting with acidic phospholipids, blocks import of precursor proteins by isolated yeast mitochondria.
Acidic phospholipids such as cardiolipin partially unfold an artificial precursor protein which consists of a mitochondrial presequence fused to mouse dihydrofolate reductase (Endo, T., and Schatz, G. (1988) EMBO J. 7, 1153-1158). We now show that import of this precursor protein into isolated yeast mitochondria is blocked by adriamycin, a drug binding to cardiolipin and other acidic phospholipids. This inhibition is lessened if the precursor's dihydrofolate reductase moiety is labilized by point mutations; inhibition is abolished altogether if the "wild-type" precursor is presented to mitochondria in a urea-denatured state. These and other observations suggest that adriamycin interferes with the generation of a translocation-competent, loose structure of the precursor protein. They imply that acidic phospholipids such as cardiolipin participate, directly or indirectly, in the translocation of this fusion protein into isolated mitochondria.
Eilers
M
M
Biocenter, University of Basel, Switzerland.
Endo
T
T
Schatz
G
G
D004317:Doxorubicin / Q000494:pharmacology*; D007700:Kinetics; D008564:Membrane Potentials; D008928:Mitochondria / Q000378:metabolism*; D010743:Phospholipids / Q000037:antagonists & inhibitors*; D014176:Protein Biosynthesis; D011993:Recombinant Fusion Proteins / Q000378:metabolism*; D011994:Recombinant Proteins / Q000378:metabolism*; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism*; D013762:Tetrahydrofolate Dehydrogenase / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic
D010743:Phospholipids; D011993:Recombinant Fusion Proteins; D011994:Recombinant Proteins; D004317:Doxorubicin; D013762:Tetrahydrofolate Dehydrogenase