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Mitochondrion. 2005 Feb;5(1):55-65.

Zinc causes loss of membrane potential and elevates reactive oxygen species in rat brain mitochondria.

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1
Department of Pharmacology, University of Pittsburgh, W1351 Biomedical Science Tower, Pittsburgh, PA 15261, USA.

Abstract

Emerging evidence suggests that Zn2+ may impair neuronal metabolism. We examined how Zn2+ affects the activity of isolated brain mitochondria fueled with glutamate + malate, succinate or glycerol 3-phosphate. Submicromolar levels of Zn2+ dissipated membrane potential and inhibited oxygen utilization in all three substrate conditions. Zn(2+)-induced depolarization was reversed by the membrane-impermeant metal chelator, EGTA, and was inhibited by uniporter blockade. Cyclosporin A did not block Zn(2+)-induced depolarization. Added Zn2+ increased accumulation of reactive oxygen species (ROS) in glutamate + malate or glycerol 3-phosphate conditions, but inhibited succinate-supported ROS accumulation. These results show that Zn2+ blocks mitochondrial function in all physiologically relevant substrate conditions.

PMID:
16060292
[Indexed for MEDLINE]
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