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Nitric oxide regulates mitochondrial respiration and cell functions by inhibiting cytochrome oxidase
1Department of Biochemistry, University of Cambridge, UK.
Abstract:
Nitric oxide (NO) reversibly inhibits mitochondrial respiration by competing with oxygen at cytochrome oxidase. Concentrations of NO measured in a range of biological systems are similar to those shown to inhibit cytochrome oxidase and mitochondrial respiration. Inhibition of NO synthesis results in a stimulation of respiration in a number of systems. It is proposed that NO exerts some of its main physiological and pathological effects on cell functions by inhibiting cytochrome oxidase. Further NO may be a physiological regulator of the affinity of mitochondrial respiration for oxygen, enabling mitochondria to act as sensors of oxygen over the physiological range.
Insights
Nitric oxide (NO) reversibly inhibits mitochondrial respiration by competing with oxygen. This suggests NO may regulate cellular oxygen sensing and physiological responses by modulating mitochondrial function.
Area of Science:
- Biochemistry
- Cellular Biology
- Physiology
Background:
- Nitric oxide (NO) is known to interact with biological systems.
- Mitochondrial respiration is a key cellular process involving cytochrome oxidase.
Purpose of the Study:
- To investigate the role of nitric oxide in regulating mitochondrial respiration.
- To explore the potential of NO as a physiological regulator of oxygen sensing in mitochondria.
Main Methods:
- The study discusses the competitive inhibition of oxygen at cytochrome oxidase by nitric oxide.
- Measurements of NO concentrations in biological systems were considered.
- The effects of inhibiting NO synthesis on respiration were observed.
Main Results:
- Nitric oxide reversibly inhibits mitochondrial respiration by competing with oxygen at cytochrome oxidase.
- Measured NO concentrations are comparable to those that inhibit mitochondrial respiration.
- Inhibition of NO synthesis leads to increased respiration in various systems.
Conclusions:
- Nitric oxide likely exerts physiological and pathological effects by inhibiting cytochrome oxidase.
- NO may function as a physiological regulator of mitochondrial oxygen affinity, enabling oxygen sensing.