Mitochondria are often regarded as a major source of reactive oxygen species (ROS) in animal cells, with H2O2 being the predominant ROS released from mitochondria; however, it has been recently demonstrated that energized brain mitochondria may act as stabilizers of H2O2 concentration (Starkov et al. [1]) based on the balance between production and the consumption of H2O2, the later of which is a function of [H2O2] and follows first order kinetics. Here we test the hypothesis that isolated skeletal muscle mitochondria, from the rat, are able to modulate [H2O2] based upon the interaction between the production of ROS, as superoxide/H2O2, and the H2O2 decomposition capacity. The compartmentalization of detection systems for H2O2 and the intramitochondrial metabolism of H2O2 leads to spacial separation between these two components of the assay system. This results in an underestimation of rates when relying solely on extramitochondrial H2O2 detection. We find that differentiating between these apparent rates found when using extramitochondrial H2O2 detection and the actual rates of metabolism is important to determining the rate constant for H2O2 consumption by mitochondria in kinetic experiments. Using the high rate of ROS production by mitochondria respiring on succinate, we demonstrate that net H2O2 metabolism by mitochondria can approach a stable steady-state of extramitochondrial [H2O2]. Importantly, the rate constant determined by extrapolation of kinetic experiments is similar to the rate constant determined as the [H2O2] approaches a steady state.
Este artigo se origina a partir do encontro da escrita de Clarice Lispector com a filosofia de Gilles Deleuze e Félix Guattari e propõe aproximações entre a literatura da escritora e os conceitos desenvolvidos pelos autores. Para Deleuze e Guattari, a literatura se faz em um plano de composição e cria perceptos e afectos através de um personagem estético; já a filosofia, tece um plano de imanência para criar seus conceitos que se constroem por meio de um personagem conceitual. Neste artigo, buscou-se discutir em que instância personagens estéticos e personagens conceituais se atravessam. Quais as ressonâncias que textos de Clarice podem provocar no campo filosófico? Para isso, foram percorridas algumas linhas criativas de sua literatura, como o devir, seguindo-as em busca de visualizar alguns conceitos sensoriais e algumas sensações conceituais que afloram da criação literária da escritora, percorrendo nela uma força filosófica que cria e mobiliza conceitos.
Este artigo apresenta uma leitura dos textos de Clarice Lispector “Perdoando Deus” e “O relatório da coisa” a partir de alguns conceitos de Gilles Deleuze e de Félix Guattari, buscando aproximar o estado epifânico das personagens clariceanas do processo de visão da personagem-vidente e demonstrar como blocos sensoriais aparecem na literatura da escritora. A partir do encontro com “coisas reveladoras”, as personagens despertam para um estado apurado de percepção que lhes deixam em contato com a sensação pura, não mediada, que seria a “coisa em si”. Através de um processo que Deleuze e Guattari chamam de “torção da língua”, a escritora subverte estruturas sintáticas e semânticas, dando a ver o invisível, fazendo da linguagem uma ferramenta do não-dito que traz à tona o acontecimento.
Mitochondria are widely recognized as a potential source of reactive oxygen species (ROS); however, mitochondria also possess a strong capacity for ROS consumption that is often underappreciated. In skeletal muscle the glutathione and thioredoxin based peroxidase systems are likely the major H2O2 consumption pathways. Here we demonstrate the thioredoxin‐based pathway is the major H2O2 consumer in isolated rat skeletal muscle mitochondria. Unlike 1‐chloro‐2,4‐dinitrobenzene, the thioredoxin reductase inhibitor auranofin does not elevate ROS production in disrupted membranes that are devoid of the capacity to consume H2O2. Inhibition of thioredoxin reductase with auranofin leads to a marked increase in apparent ROS production but no change in mitochondrial bioenergetic characteristics (oxygen consumption, membrane potential, %NAD(P)H). Moreover, auranofin also inhibits the capacity for H2O2 consumption by isolated mitochondria and does not appear to act through the inhibition of the glutathione reduction system. We conclude that the apparent increase is H2O2 release by treatment with auranofin is due to impaired matrix level thioredoxin‐dependent H2O2 consumption and not reflective of an activation of ROS production.
Grant Funding Source: Supported by Canada Research Chairs (CRC), CFI, Manitoba Research and Innovation Fund and NSERC
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