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

被引：160

作者：

Dineley, KE ^{[1
]}

Richards, LL ^{[1
]}

Votyakova, TV ^{[1
]}

Reynolds, IJ ^{[1
]}

机构：

[1] Univ Pittsburgh, Dept Pharmacol, Pittsburgh, PA 15261 USA

来源：

MITOCHONDRION | 2005年 / 5卷 / 01期

关键词：

ROS; spectrofluorometry; permeability transition; calcium uniporter; excitotoxicity; neurodegeneration;

D O I：

10.1016/j.mito.2004.11.001

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

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. Zn2+-induced depolarization was reversed by the membrane-impermeant metal chelator, EGTA, and was inhibited by uniporter blockade. Cyclosporin A did not block Zn2+-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. (C) 2004 Elsevier B.V. and Mitochondria Research Society. All rights reserved.

引用

页码：55 / 65

页数：11

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