| Literature DB >> 19528654 |
Tracy A Prime1, Frances H Blaikie, Cameron Evans, Sergiy M Nadtochiy, Andrew M James, Christina C Dahm, Dario A Vitturi, Rakesh P Patel, C Robin Hiley, Irina Abakumova, Raquel Requejo, Edward T Chouchani, Thomas R Hurd, John F Garvey, Cormac T Taylor, Paul S Brookes, Robin A J Smith, Michael P Murphy.
Abstract
Nitric oxide (NO(*)) competitively inhibits oxygen consumption by mitochondria at cytochrome c oxidase and S-nitrosates thiol proteins. We developed mitochondria-targeted S-nitrosothiols (MitoSNOs) that selectively modulate and protect mitochondrial function. The exemplar MitoSNO1, produced by covalently linking an S-nitrosothiol to the lipophilic triphenylphosphonium cation, was rapidly and extensively accumulated within mitochondria, driven by the membrane potential, where it generated NO(*) and S-nitrosated thiol proteins. MitoSNO1-induced NO(*) production reversibly inhibited respiration at cytochrome c oxidase and increased extracellular oxygen concentration under hypoxic conditions. MitoSNO1 also caused vasorelaxation due to its NO(*) generation. Infusion of MitoSNO1 during reperfusion was protective against heart ischemia-reperfusion injury, consistent with a functional modification of mitochondrial proteins, such as complex I, following S-nitrosation. These results support the idea that selectively targeting NO(*) donors to mitochondria is an effective strategy to reversibly modulate respiration and to protect mitochondria against ischemia-reperfusion injury.Entities:
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Year: 2009 PMID： 19528654 PMCID： PMC2696550 DOI： 10.1073/pnas.0903250106
Source DB: PubMed Journal: Proc Natl Acad Sci U S A ISSN： 0027-8424 Impact factor: 11.205