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Simultaneous Measurement of Superoxide/Hydrogen Peroxide and NADH Production by Flavin-containing Mitochondrial Dehydrogenases
Published on: February 24, 2018
Mitochondria in homeostasis of reactive oxygen species in cell, tissues, and organism
1Department of Membrane Transport Biophysics, No. 75, Institute of Physiology, Academy of Sciences of the Czech Republic, Vídenská 1083, CZ 14220 Prague, Czech Republic. jezek@biomed.cas.cz
Abstract:
The recent knowledge on mitochondria as the substantial source of reactive oxygen species, namely superoxide and hydrogen peroxide efflux from mitochondria, is reviewed, as well as nitric oxide and subsequent peroxynitrite generation in mitochondria and their effects. The reactive oxygen species formation in extramitochondrial locations, in peroxisomes, by cytochrome P450, and NADPH oxidase reaction, is also briefly discussed. Conditions are pointed out under which mitochondria represent the major ROS source for the cell: higher percentage of non-phosphorylating and coupled mitochondria, in vivo oxygen levels leading to increased intensity of the reverse electron transport in the respiratory chain, and nitric oxide effects on the redox state of cytochromes. We formulate hypotheses on the crucial role of ROS generated in mitochondria for the whole cell and organism, in concert with extramitochondrial ROS and antioxidant defense. We hypothesize that a sudden decline of mitochondrial ROS production converts cells or their microenvironment into a "ROS sink" represented by the instantly released excessive capacity of ROS-detoxification mechanisms. A partial but immediate decline of mitochondrial ROS production may be triggered by activation of mitochondrial uncoupling, specifically by activation of recruited or constitutively present uncoupling proteins such as UCP2, which may counterbalance the mild oxidative stress.
Insights
Mitochondria are key sources of reactive oxygen species (ROS), influencing cellular health. Declines in mitochondrial ROS production may shift cells into a ROS-detoxifying state, potentially mediated by uncoupling proteins like UCP2.
Area of Science:
- Biochemistry
- Cell Biology
- Physiology
Background:
- Mitochondria are significant producers of reactive oxygen species (ROS), including superoxide and hydrogen peroxide.
- Extramitochondrial ROS sources like peroxisomes, cytochrome P450, and NADPH oxidase also contribute to cellular oxidative stress.
- Nitric oxide and peroxynitrite generation within mitochondria are critical factors affecting cellular function.
Purpose of the Study:
- To review current knowledge on mitochondrial ROS production and its cellular effects.
- To identify conditions under which mitochondria become the primary ROS source.
- To hypothesize the role of mitochondrial ROS in cellular redox balance and the consequences of its decline.
Main Methods:
- Literature review of mitochondrial ROS generation.
- Analysis of factors influencing mitochondrial ROS production (e.g., oxygen levels, respiratory chain activity, nitric oxide).
- Formulation of hypotheses regarding ROS signaling and cellular adaptation.
Main Results:
- Mitochondria are substantial sources of superoxide and hydrogen peroxide.
- Conditions favoring mitochondrial ROS production include non-phosphorylating mitochondria, high oxygen, and nitric oxide interactions.
- Hypothesized that reduced mitochondrial ROS production can create a cellular 'ROS sink' via detoxification mechanisms.
Conclusions:
- Mitochondrial ROS plays a crucial role in cellular signaling alongside extramitochondrial ROS and antioxidant defenses.
- A sudden decrease in mitochondrial ROS may lead to cells acting as ROS scavengers.
- Mitochondrial uncoupling proteins, such as UCP2, may trigger a decline in ROS production, counteracting mild oxidative stress.
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