Production of reactive XXXX species by mitochondria: central role of complex III.

@entity2125 @entity2227 @entity274 @entity63 @entity3788 @entity26 @entity8581 @entity5910 @entity741 @entity12609 @entity35 @entity2388
The mitochondrial respiratory chain is a major source of reactive @entity26 species (ROS) under pathological conditions including @entity741 and reperfusion. Limitation of electron transport by the inhibitor @entity3788 immediately before @entity63 decreases the production of ROS in cardiac myocytes and reduces damage to mitochondria. We asked if ROS generation by intact mitochondria during the oxidation of complex I substrates ( @entity2227 , @entity2388 / @entity5910 ) occurred from complex I or III. ROS production by mitochondria of @entity35 hearts and corresponding submitochondrial particles was studied. ROS were measured as @entity274 using the amplex red assay. In mitochondria oxidizing complex I substrates, @entity3788 inhibition did not increase @entity274 . Oxidation of complex I or II substrates in the presence of @entity8581 markedly increased @entity274 . @entity3788 prevented @entity8581 -induced @entity274 production in mitochondria with complex I substrates but not with complex II substrates. @entity12609 scavenged @entity274 . In contrast to intact mitochondria, blockade of complex I with @entity3788 markedly increased @entity274 production from submitochondrial particles oxidizing the complex I substrate @entity2125 . ROS are produced from complex I by the @entity2125 dehydrogenase located in the matrix side of the inner membrane and are dissipated in mitochondria by matrix antioxidant defense. However, in submitochondrial particles devoid of antioxidant defense ROS from complex I are available for detection. In mitochondria, complex III is the principal site for ROS generation during the oxidation of complex I substrates, and @entity3788 protects by limiting electron flow into complex III.
