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Updated: Aug 16, 2026

Application of Genetically Encoded Fluorescent Nitric Oxide (NO•) Probes, the geNOps, for Real-time Imaging of NO• Signals in Single Cells
Published on: March 16, 2017
Mitochondrial nitric oxide synthase
1Department of Anesthesiology, University of Rochester Medical Center, Box 604, 601 Elmwood Avenue, Rochester, NY 14642, USA. paul_brookes@urmc.rochester.edu
Abstract:
Nitric oxide (NO*) can bind to and inhibit the terminal enzyme of the mitochondrial respiratory chain, cytochrome c oxidase (complex IV). In vivo, NO* is made by the NO* synthase (NOS) family of enzymes, and considerable debate has recently arisen regarding a NOS inside mitochondria (termed 'mtNOS'). Such an enzyme is an intriguing proposition, since it affords unique organelle-based regulatory mechanisms for NO* synthesis, and has considerable implications for mitochondrial function. This review serves to discuss some of the current issues regarding mtNOS, such as its isoform identity, the availability of co-factors and substrates within the organelle, and potential physiological vs. pathological roles for the enzyme, all within the broader context of mitochondrial regulation by NO*.
Insights
Mitochondria may contain nitric oxide synthase (NOS) enzymes, termed mtNOS, which regulate mitochondrial function. This review explores the evidence, co-factor availability, and roles of mtNOS in health and disease.
Area of Science:
- Biochemistry
- Cell Biology
- Mitochondrial Physiology
Background:
- Nitric oxide (NO*) is a signaling molecule that inhibits cytochrome c oxidase (complex IV) in the mitochondrial respiratory chain.
- The existence and function of a nitric oxide synthase (NOS) within mitochondria (mtNOS) are subjects of ongoing scientific debate.
- mtNOS presents unique organelle-based regulatory mechanisms for NO* synthesis with significant implications for mitochondrial function.
Purpose of the Study:
- To review current issues and evidence regarding the existence and role of mitochondrial nitric oxide synthase (mtNOS).
- To discuss the isoform identity, co-factor/substrate availability, and physiological/pathological roles of mtNOS.
- To contextualize mtNOS within the broader scope of NO*-mediated mitochondrial regulation.
Main Methods:
- Literature review of existing research on nitric oxide synthase (NOS) and its presence in mitochondria.
- Analysis of evidence for mtNOS isoform identity and localization.
- Discussion of biochemical requirements (co-factors, substrates) for mtNOS activity within the mitochondrial matrix.
Main Results:
- Evidence suggests the potential presence and activity of NOS enzymes within mitochondria.
- The precise isoform identity of mtNOS remains under investigation.
- The availability of essential co-factors and substrates for mtNOS within mitochondria is a critical factor for its function.
Conclusions:
- The existence of mtNOS offers novel insights into organelle-specific regulation of cellular respiration and NO* signaling.
- Understanding mtNOS is crucial for elucidating its physiological roles in normal function and its pathological involvement in disease.
- Further research is needed to definitively establish the identity and functional significance of mtNOS in mitochondrial regulation.
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