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线粒体外膜蛋白米托奈德（mitoNEET）的[2Fe-2S]簇具有一个受氧调节的一氧化氮通道。

The [2Fe-2S] cluster of mitochondrial outer membrane protein mitoNEET has an O-regulated nitric oxide access tunnel.

作者信息

Hoang Thao Nghi, Wu-Lu Meritxell, Collauto Alberto, Hagedoorn Peter-Leon, Alexandru Madalina, Henschel Maike, Kordasti Shahram, Mroginski Maria Andrea, Roessler Maxie M, Ebrahimi Kourosh H

机构信息

Institute of Pharmaceutical Science, King's College London, UK.

Department of Pharmacy, Da Nang University of Medical Technology and Pharmacy, Vietnam.

出版信息

FEBS Lett. 2025 Apr;599(7):952-970. doi: 10.1002/1873-3468.15097. Epub 2025 Jan 5.

DOI:10.1002/1873-3468.15097
PMID:39757450
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11995679/
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 O 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 O protection of the mitoNEET [2Fe-2S] cluster, a new paradigm in understanding the importance of [Fe-S] clusters for gasotransmitter signal transduction in eukaryotes.

摘要

线粒体外膜铁硫（[Fe-S]）蛋白米托萘醌已被广泛研究，它是抗炎和2型糖尿病药物吡格列酮的作用靶点，也是一种影响线粒体呼吸速率的蛋白。尽管过去进行了大量研究，但其分子功能尚未被发现。在此，我们采用跨学科方法，发现了一个明确的一氧化氮（NO）进入米托萘醌[2Fe-2S]簇的位点。我们发现氧气和吡格列酮会阻止NO进入该簇，这表明米托萘醌[2Fe-2S]簇在线粒体信号转导中具有分子功能。我们的发现暗示了一条新途径，通过该途径线粒体可以通过对米托萘醌[2Fe-2S]簇的氧气保护来感知缺氧，这是理解[Fe-S]簇对真核生物中气体递质信号转导重要性的一个新范例。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8e75/11995679/d3e2a8b88138/FEB2-599-952-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8e75/11995679/36bf048d7a0d/FEB2-599-952-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8e75/11995679/5888e4681a4f/FEB2-599-952-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8e75/11995679/554420d2822a/FEB2-599-952-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8e75/11995679/a336ab11b8ef/FEB2-599-952-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8e75/11995679/0b264eeb942f/FEB2-599-952-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8e75/11995679/d3e2a8b88138/FEB2-599-952-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8e75/11995679/36bf048d7a0d/FEB2-599-952-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8e75/11995679/5888e4681a4f/FEB2-599-952-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8e75/11995679/554420d2822a/FEB2-599-952-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8e75/11995679/a336ab11b8ef/FEB2-599-952-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8e75/11995679/0b264eeb942f/FEB2-599-952-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8e75/11995679/d3e2a8b88138/FEB2-599-952-g005.jpg

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Interplay between hypoxia inducible Factor-1 and mitochondria in cardiac diseases.缺氧诱导因子-1 与心脏疾病中线粒体的相互作用。
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Biochemical and cellular characterization of the CISD3 protein: Molecular bases of cluster release and destabilizing effects of nitric oxide.
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J Biol Chem. 2024 Mar;300(3):105745. doi: 10.1016/j.jbc.2024.105745. Epub 2024 Feb 12.
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MitoNEET Provides Cardioprotection via Reducing Oxidative Damage and Conserving Mitochondrial Function.MitoNEET 通过减少氧化损伤和维持线粒体功能提供心脏保护。
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Ancient complexes of iron and sulfur modulate oncogenes and oncometabolism.古老的铁硫复合物调节癌基因和致癌代谢。
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