Increased mitochondrial matrix-directed superoxide production by fatty acid hydroperoxides in skeletal muscle mitochondria
Increased mitochondrial matrix-directed superoxide production by fatty acid hydroperoxides in skeletal muscle mitochondria
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DOI：
10.1016/j.freeradbiomed.2010.12.014
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发表时间：
2011-03-01
影响因子：
7.4
通讯作者：
Van Remmen, Holly
中科院分区：
文献类型：
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作者：
Bhattacharya, Arunabh;Lustgarten, Michael;Van Remmen, Holly
先前的研究表明，肌肉萎缩与线粒体功能障碍和线粒体活性氧产生速率增加有关。我们最近证明，脂肪酸氢过氧化物（FA-OOHs）显着升高，从萎缩的肌肉中分离的线粒体。本研究的目的是确定FA-OOH是否可以改变骨骼肌线粒体功能。我们发现FA-OOHs（在低微摩尔浓度下）诱导线粒体功能障碍，通过ATP产生速率、氧消耗和呼吸链复合物和III活性的降低来评估。使用的方法来区分超氧化物释放的矩阵和向膜间空间，我们表明，FA-OOHs显着提高氧化应激的线粒体基质（而不是膜间空间），与复合物I作为超氧化物生产的主要网站（最有可能从泛醌结合位点的上游，但下游的黄素结合位点的铁硫簇）。我们的研究结果首次表明FA-OOH是骨骼肌线粒体中线粒体功能和氧化应激的重要调节剂，并可能在与FA-OOH生成增加相关的肌肉萎缩中发挥重要作用，例如，去神经诱导的肌肉萎缩(C)2010年由Elsevier Inc.出版
Previous studies have shown that muscle atrophy is associated with mitochondrial dysfunction and an increased rate of mitochondrial reactive oxygen species production. We recently demonstrated that fatty acid hydroperoxides (FA-OOHs) are significantly elevated in mitochondria isolated from atrophied muscles. The purpose of this study was to determine whether FA-OOHs can alter skeletal muscle mitochondrial function. We found that FA-OOHs (at low-micromolar concentrations) induce mitochondrial dysfunction assessed by a decrease in the rate of ATP production, oxygen consumption, and activity of respiratory chain complexes land Ill. Using methods to distinguish superoxide release toward the matrix and toward the intermembrane space, we demonstrate that FA-OOHs significantly elevate oxidative stress in the mitochondrial matrix (and not the intermembrane space), with complex I as the major site of superoxide production (most probably from a site upstream of the ubiquinone binding site but downstream from the flavin binding site the-iron sulfur clusters). Our results are the first to indicate that FA-OOHs are, important modulators of mitochondrial function and oxidative stress in skeletal muscle mitochondria and may play an important role in muscle atrophies that are associated with increased generation of FA-OOHs, e.g., denervation-induced muscle atrophy. (C) 2010 Published by Elsevier Inc.