Manganese Enhances Mitochondrial H2O2 Emission by Different Mechanisms

Autor: Erik Bonke, Klaus Zwicker, Ilka Siebels, Stefan Dröse
Rok vydání: 2016
Předmět:
Zdroj: Free Radical Biology and Medicine. 100:S20
ISSN: 0891-5849
Popis: The mitochondrial respiratory chain is a major source of cellular reactive oxygen species (ROS). Recent data indicate that beside the established H 2 O 2 /O 2 ●– -generators NADH-ubiquinone- (complex I) and the ubiquinone-cytrochrome c -oxidoreductase (complex III), additional sources significantly contribute to the overall ROS production. These include the oxoglutarate dehydrogenase complex and the succinate dehydrogenase (complex II; SDH). The latter was shown to produce mainly H 2 O 2 from its FAD site. More recently manganese toxicity in the central nervous system has been linked to an elevated ROS production by complex II. However, the molecular mechanism as well as the distinct site of origin remained elusive. In this study with submitochondrial particles (SMP) and isolated rat heart mitochondria (RHM) we confirmed an inducing effect of manganese on ROS production by complex II. Furthermore, we tracked down H 2 O 2 /O 2 ●– -to be derived mainly from the ubiquinone binding site. In RHM, manganese additionally acted as a potent inducer of mitochondrial permeability transition, and hence potentiated the emission of H 2 O 2 from ‘substrate’ oxidoreductases of the Krebs cycle. Moreover, manganese generally led to an enhanced emission of hydrogen peroxide due to its accelerating effect on superoxide dismutation. These findings highlight the complex effects of manganese on mitochondrial H 2 O 2 emission. They also warrant further explorations aiming to understand/predict the functional consequences of H 2 O 2 /O 2 ●– formed at distinct sites of SDH.
Databáze: OpenAIRE
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