A mitochondria-targeted S-nitrosothiol modulates respiration, nitrosates thiols, and protects against ischemia-reperfusion injury

Academic Article


  • Nitric oxide (NO•) competitively inhibits oxygen consumption by mitochondria at cytochrome c oxidase and S-nitrosates thiol proteins. Wedeveloped 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.
  • Digital Object Identifier (doi)

    Author List

  • Prime TA; Blaikie FH; Evans C; Nadtochiy SM; James AM; Dahm CC; Vitturi DA; Patel RP; Hileye CR; Abakumova I
  • Start Page

  • 10764
  • End Page

  • 10769
  • Volume

  • 106
  • Issue

  • 26