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Updated: Jun 3, 2025

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
The [2Fe-2S] cluster of mitochondrial outer membrane protein mitoNEET has an O2-regulated nitric oxide access tunnel
Thao Nghi Hoang1,2, Meritxell Wu-Lu3, Alberto Collauto4
1Institute of Pharmaceutical Science, King's College London, UK.
Abstract:
The mitochondrial outer membrane iron-sulphur ([Fe-S]) protein mitoNEET has been extensively studied as a target of the anti-inflammatory and type-2 diabetes drug pioglitazone and as a protein affecting mitochondrial respiratory rate. Despite these extensive past studies, its molecular function has yet to be discovered. Here, we applied an interdisciplinary approach and discovered an explicit nitric oxide (NO) access site to the mitoNEET [2Fe-2S] cluster. We found that O2 and pioglitazone block NO access to the cluster, suggesting a molecular function for the mitoNEET [2Fe-2S] cluster in mitochondrial signal transduction. Our discovery hints at a new pathway via which mitochondria can sense hypoxia through O2 protection of the mitoNEET [2Fe-2S] cluster, a new paradigm in understanding the importance of [Fe-S] clusters for gasotransmitter signal transduction in eukaryotes.
Insights
Researchers discovered a nitric oxide (NO) access site on the mitoNEET protein
Area of Science:
- Mitochondrial biology
- Biochemistry
- Cell signaling
Background:
- The iron-sulphur protein mitoNEET is involved in mitochondrial respiration and targeted by pioglitazone.
- Its precise molecular function remains unknown despite extensive research.
Purpose of the Study:
- To elucidate the molecular function of mitoNEET.
- To investigate the interaction of mitoNEET with nitric oxide (NO).
Main Methods:
- Interdisciplinary approach combining biophysical and biochemical techniques.
- Investigated the effect of oxygen and pioglitazone on NO binding to the mitoNEET [2Fe-2S] cluster.
Main Results:
- Identified a specific site for nitric oxide (NO) access to the mitoNEET [2Fe-2S] cluster.
- Oxygen (O2) and pioglitazone were found to block NO access to the cluster.
- This suggests a role for mitoNEET in sensing hypoxia and NO signaling.
Conclusions:
- MitoNEET's [2Fe-2S] cluster is involved in mitochondrial signal transduction.
- Mitochondria may sense hypoxia via O2-mediated protection of the mitoNEET cluster.
- This highlights a new role for [Fe-S] clusters in gasotransmitter signaling.
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