Calcium-Dependent Interaction of Nitric Oxide Synthase with Cytochrome c Oxidase: Implications for Brain Bioenergetics.

Calcium-Dependent Interaction of Nitric Oxide Synthase with Cytochrome c Oxidase: Implications for Brain Bioenergetics.
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一氧化氮合酶与细胞色素 c 氧化酶的钙依赖性相互作用:对脑生物能学的影响。

DOI:
10.3390/brainsci13111534
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发表时间:
2023-10-31
期刊:
影响因子:
3.3
通讯作者:
--
中科院分区:
医学4区
文献类型:
--
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靶向一氧化氮的产生与维持细胞能量产生、防止氧化应激、调节细胞死亡和促进神经保护有关。本研究旨在表征一氧化氮合酶与线粒体蛋白的推定相互作用。本研究的主要发现是当钙离子存在时,细胞色素c氧化酶(CCO)亚基IV (CCOIV)与脑线粒体NOS直接相关。CCOIV的基质侧与NOS的n端结合,支持废除绑定的抗体分子的n端NOS。提供了证据支持CCOIV之间的交互和NOS的coimmunoprecipitation号从detergent-solubilized整个老鼠大脑线粒体抗体CCOIV从原油和CCOIV coimmunoprecipitation大脑号准备使用抗体NOS。CCOIV域与NOS被确认使用一系列重叠的肽来源于主CCOIV序列。由于钙离子不仅激活NOS,而且促进NOS与CCOIV的对接,本研究指出了一种通过钙变化控制生物能学的动力学机制,从而使生物能学适应细胞需求。
Targeted nitric oxide production is relevant for maintaining cellular energy production, protecting against oxidative stress, regulating cell death, and promoting neuroprotection. This study aimed to characterize the putative interaction of nitric-oxide synthase with mitochondrial proteins. The primary finding of this study is that cytochrome c oxidase (CCO) subunit IV (CCOIV) is associated directly with NOS in brain mitochondria when calcium ions are present. The matrix side of CCOIV binds to the N-terminus of NOS, supported by the abrogation of the binding by antibodies towards the N-terminus of NOS. Evidence supporting the interaction between CCOIV and NOS was provided by the coimmunoprecipitation of NOS from detergent-solubilized whole rat brain mitochondria with antibodies to CCOIV and the coimmunoprecipitation of CCOIV from crude brain NOS preparations using antibodies to NOS. The CCOIV domain that interacts with NOS was identified using a series of overlapping peptides derived from the primary sequence of CCOIV. As calcium ions not only activate NOS, but also facilitate the docking of NOS to CCOIV, this study points to a dynamic mechanism of controlling the bioenergetics by calcium changes, thereby adapting bioenergetics to cellular demands.
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