Calcium-Dependent Interaction of Nitric Oxide Synthase with Cytochrome <i>c</i> Oxidase: Implications for Brain Bioenergetics
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 prim...
| Main Authors: | , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2023-10-01
|
| Series: | Brain Sciences |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2076-3425/13/11/1534 |
| _version_ | 1797459990181576704 |
|---|---|
| author | Virginia Haynes Cecilia Giulivi |
| author_facet | Virginia Haynes Cecilia Giulivi |
| author_sort | Virginia Haynes |
| collection | DOAJ |
| description | 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 <i>c</i> 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 <i>N</i>-terminus of NOS, supported by the abrogation of the binding by antibodies towards the <i>N</i>-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. |
| first_indexed | 2024-03-09T16:58:50Z |
| format | Article |
| id | doaj.art-a16cce62b2f24f3b8fc27b9b8dd05000 |
| institution | Directory Open Access Journal |
| issn | 2076-3425 |
| language | English |
| last_indexed | 2024-03-09T16:58:50Z |
| publishDate | 2023-10-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Brain Sciences |
| spelling | doaj.art-a16cce62b2f24f3b8fc27b9b8dd050002023-11-24T14:32:38ZengMDPI AGBrain Sciences2076-34252023-10-011311153410.3390/brainsci13111534Calcium-Dependent Interaction of Nitric Oxide Synthase with Cytochrome <i>c</i> Oxidase: Implications for Brain BioenergeticsVirginia Haynes0Cecilia Giulivi1School of Veterinary Medicine, Department Molecular Biosciences, University of California Davis, Davis, CA 95616, USASchool of Veterinary Medicine, Department Molecular Biosciences, University of California Davis, Davis, CA 95616, USATargeted 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 <i>c</i> 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 <i>N</i>-terminus of NOS, supported by the abrogation of the binding by antibodies towards the <i>N</i>-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.https://www.mdpi.com/2076-3425/13/11/1534mitochondrianitric oxidenitric oxide synthaseprotein–protein interactionComplex IVbioenergetics |
| spellingShingle | Virginia Haynes Cecilia Giulivi Calcium-Dependent Interaction of Nitric Oxide Synthase with Cytochrome <i>c</i> Oxidase: Implications for Brain Bioenergetics Brain Sciences mitochondria nitric oxide nitric oxide synthase protein–protein interaction Complex IV bioenergetics |
| title | Calcium-Dependent Interaction of Nitric Oxide Synthase with Cytochrome <i>c</i> Oxidase: Implications for Brain Bioenergetics |
| title_full | Calcium-Dependent Interaction of Nitric Oxide Synthase with Cytochrome <i>c</i> Oxidase: Implications for Brain Bioenergetics |
| title_fullStr | Calcium-Dependent Interaction of Nitric Oxide Synthase with Cytochrome <i>c</i> Oxidase: Implications for Brain Bioenergetics |
| title_full_unstemmed | Calcium-Dependent Interaction of Nitric Oxide Synthase with Cytochrome <i>c</i> Oxidase: Implications for Brain Bioenergetics |
| title_short | Calcium-Dependent Interaction of Nitric Oxide Synthase with Cytochrome <i>c</i> Oxidase: Implications for Brain Bioenergetics |
| title_sort | calcium dependent interaction of nitric oxide synthase with cytochrome i c i oxidase implications for brain bioenergetics |
| topic | mitochondria nitric oxide nitric oxide synthase protein–protein interaction Complex IV bioenergetics |
| url | https://www.mdpi.com/2076-3425/13/11/1534 |
| work_keys_str_mv | AT virginiahaynes calciumdependentinteractionofnitricoxidesynthasewithcytochromeicioxidaseimplicationsforbrainbioenergetics AT ceciliagiulivi calciumdependentinteractionofnitricoxidesynthasewithcytochromeicioxidaseimplicationsforbrainbioenergetics |