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Journal of Experimental Biology, Vol 199, Issue 7 1447-1454, Copyright © 1996 by Company of Biologists

JOURNAL ARTICLES

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

Y Moriyama
Division of Marine Molecular Biology, Graduate School of Gene Sciences, Hiroshima University, Japan.

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.

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