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Outer Membrane Lysis Increases Accessibility of Cationic Drugs to the Inner Mitochondrial Membrane

  • Joyce J. Diwan
  • Carmen A. Mannella
  • Teresa Haley
  • R. Bawa
  • Helen H. Yune

Summary

The cationic anticancer drugs adriamycin and MGBG, and the polyamine spermidine, inhibit mitochondrial respiration. This inhibitory effect depends on the integrity of the outer mitochondrial membrane. Lysis of the outer membrane enhances inhibitory interactions of the organic cations with the respiratory chain. Addition of digitonin to Iyse the outer membrane also results in an increment of uptake of isotopically labeled spermidine and MGBG, consistent with rapid penetration of the outer membrane barrier. Subsequent to outer membrane lysis, a slower respiration dependent uptake of spermidine and MGBG is seen, which appears to reflect transport across the inner membrane into the mitochondrial matrix. 14C-Iabeled daunomycin, a structural analog of adriamycin, rapidly binds to the mitochondria by a mechanism which includes non-ionic interactions.

Keywords

Outer Membrane Organic Cation Outer Mitochondrial Membrane Distribution Space Water Space 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Abbreviations

MGBG

methylglyoxal-bis(guanylhydrazone)

CCCP

carbonyl cyanide m-chlorophenylhydrazone

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Copyright information

© Plenum Press, New York 1987

Authors and Affiliations

  • Joyce J. Diwan
    • 1
  • Carmen A. Mannella
    • 1
    • 2
  • Teresa Haley
    • 1
  • R. Bawa
    • 1
  • Helen H. Yune
    • 1
  1. 1.Biology DepartmentRensselaer Polytechnic InstituteTroyUSA
  2. 2.Wadsworth Center for Laboratories and Research State of New York Department of Health, and School of Public Health SciencesState University of New York at AlbanyAlbanyUSA

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