Membrane energization by proton pumps is important for compartmentalization of drugs and toxins: A new type of active transport

Yoshinori Moriyama

Research output: Contribution to journalArticle

21 Citations (Scopus)

Abstract

Many organelles are energized by proton pumps: mitochondria form an inside-negative membrane potential by means of the respiratory chain and endomembrane structures, such as lysosomes and synaptic vesicles, establish an internal acidic pH by means of a vacuolar-type H+-ATPase (V- ATPase). Various amphipathic drugs such as local anesthetics and neuron blockers are accumulated in acidic organelles upon energization by proton pumps. However, this process does not require any transporters specific for the drugs: these drugs penetrate through the lipid bilayer against a concentration gradient so as to accumulate inside the energized organelles. Essentially the same transport process takes place in liposomes that have been reconstituted with purified V- or F-ATPase. Various hydrophobic cations are also accumulated in mitochondria by a similar mechanism. The energy-dependent but transporter- independent accumulation does not belong to the known transport categories and seems to represent a new type of transport which may be important for understanding the mode of action of drugs and toxins.

Original languageEnglish
Pages (from-to)1447-1454
Number of pages8
JournalJournal of Experimental Biology
Volume199
Issue number7
Publication statusPublished - Jul 1996
Externally publishedYes

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Keywords

  • compartmentalization
  • drug
  • F-ATPase
  • proton pump
  • toxin
  • V-ATPase

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Agricultural and Biological Sciences (miscellaneous)

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