Sites of reactive oxygen species generation by mitochondria oxidizing different substrates.
Sites of reactive oxygen species generation by mitochondria oxidizing different substrates.
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DOI：
10.1016/j.redox.2013.04.005
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发表时间：
2013
期刊：
影响因子：
11.4
通讯作者：
Brand MD
中科院分区：
文献类型：
--
作者：
Quinlan CL;Perevoshchikova IV;Hey-Mogensen M;Orr AL;Brand MD
线粒体自由基的产生在氧化还原信号、衰老和疾病中很重要，但不同产生位点的相对贡献尚不清楚。我们分析了在没有添加抑制剂的情况下，大鼠骨骼肌线粒体中不同定义位点氧化各种常规底物的超氧化物/H2O2产生率：琥珀酸盐；甘油3 -磷酸;棕榈酰基肉碱加肉碱；或者谷氨酸加苹果酸盐。在所有情况下，估计费率的总和完全反映了测量的总费率。有两个惊人的结果。首先，总的速率在不同的底物之间有一个数量级的差异。其次，不同底物对每个位点的相对贡献差异很大。在琥珀酸盐氧化过程中，大部分超氧化物产生于配合物I的醌还原位点（IQ位点），配合物I的黄素位点（IF位点）和配合物III的醌氧化位点（iiiiq位点）也有少量贡献。然而，以谷氨酸加苹果酸盐为底物时，位点IQ几乎没有贡献，其产量由位点IF、位点iiiiq和2-氧葡萄糖酸脱氢酶共享。以棕榈酰基肉碱为底物时，复合体II中的黄素位点（IIF位点）是主要的贡献位点（以及IF位点和iiico位点）；以3-磷酸甘油为底物时，包括甘油3-磷酸脱氢酶在内的5个不同位点都有贡献。因此，在分离的线粒体中，特定位点对活性氧产生的相对和绝对贡献很大程度上取决于被氧化的底物，在细胞和体内可能也是如此。线粒体氧化四种底物组合，从六个确定的位点生成超氧化物/H2O2。线粒体超氧化物/H2O2的绝对速率取决于被氧化的底物。在不同的底物中，超氧化物/H2O2特异位点的相对贡献差异很大。
Mitochondrial radical production is important in redox signaling, aging and disease, but the relative contributions of different production sites are poorly understood. We analyzed the rates of superoxide/H2O2 production from different defined sites in rat skeletal muscle mitochondria oxidizing a variety of conventional substrates in the absence of added inhibitors: succinate; glycerol 3-phosphate; palmitoylcarnitine plus carnitine; or glutamate plus malate. In all cases, the sum of the estimated rates accounted fully for the measured overall rates. There were two striking results. First, the overall rates differed by an order of magnitude between substrates. Second, the relative contribution of each site was very different with different substrates. During succinate oxidation, most of the superoxide production was from the site of quinone reduction in complex I (site IQ), with small contributions from the flavin site in complex I (site IF) and the quinol oxidation site in complex III (site IIIQo). However, with glutamate plus malate as substrate, site IQ made little or no contribution, and production was shared between site IF, site IIIQo and 2-oxoglutarate dehydrogenase. With palmitoylcarnitine as substrate, the flavin site in complex II (site IIF) was a major contributor (together with sites IF and IIIQo), and with glycerol 3-phosphate as substrate, five different sites all contributed, including glycerol 3-phosphate dehydrogenase. Thus, the relative and absolute contributions of specific sites to the production of reactive oxygen species in isolated mitochondria depend very strongly on the substrates being oxidized, and the same is likely true in cells and in vivo. Mitochondria oxidizing four substrate combinations make superoxide/H2O2 from six defined sites. The absolute rates of mitochondrial superoxide/H2O2 depend on the substrate oxidized. The relative contributions of specific sites of superoxide/H2O2 vary greatly between substrates.
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影响因子：
4.8
作者：
Orr, Adam L.;Quinlan, Casey L.;Brand, Martin D.
通讯作者：
Brand, Martin D.
DOI：
10.1042/bj20081386
发表时间：
2009-01-01
期刊：
The Biochemical journal
影响因子：
--
作者：
Murphy MP
通讯作者：
Murphy MP
DOI：
10.1073/pnas.0510977103
发表时间：
2006-05-16
影响因子：
11.1
作者：
Kussmaul, Lothar;Hirst, Judy
通讯作者：
Hirst, Judy
影响因子：
4.8
作者：
Seifert, Erin L.;Estey, Carmen;Harper, Mary-Ellen
通讯作者：
Harper, Mary-Ellen
DOI：
10.1046/j.1432-1033.2002.03204.x
发表时间：
2002-10-01
期刊：
EUROPEAN JOURNAL OF BIOCHEMISTRY
影响因子：
--
作者：
Bunik, VI;Sievers, C
通讯作者：
Sievers, C