Nitric oxide regulation of mitochondrial oxygen consumption II: molecular mechanism and tissue physiology

This review describes the molecular mechanism of this interaction and the consequences for its likely physiological role

Chris E. Cooper


Scholarcy highlights

  • Nitric oxide is an intercellular signaling molecule; among its many and varied roles are the control of blood flow and blood pressure via activation of the heme enzyme, soluble guanylate cyclase
  • Nitric oxide is known as an intercellular messenger, synthesized in mammalian systems from arginine, NADPH, and oxygen by the NO synthase class of enzymes. It has a wide range of physiological functions, most notably the control of blood pressure and blood flow mediated by the production of cGMP via its activation of the heme enzyme, soluble guanylate cyclase
  • Just over a decade ago, several groups demonstrated that the primary target for NO interactions with mammalian mitochondria is at the level of the oxygen-consuming enzyme, cytochrome c oxidase
  • The important consequence of this when studying the interaction of NO in physiology is that effects can occur via changes in redox state of enzyme and pathway intermediates, as well as via a direct effect on oxygen consumption and energy transduction
  • We have argued previously that given the ubiquity of NO signaling in biology and its structural similarity to oxygen, all metalloproteins that react with oxygen may have evolved mechanisms to prevent being inhibited by NO
  • It is intriguing that the turtle brain, which is highly resistant to hypoxia, has an almost linear dependence of cytochrome oxidase redox state on a reduction in oxygen delivery, as opposed to the “threshold” effect seen in mammals ; this implies that cytochrome oxidase may always be oxygen-limited in the turtle, as might be expected were NO to be present at levels to inhibit the enzyme
  • An increase in cerebral blood flow is generally accompanied by an increase in Nitric oxide levels; NO inhibition of cytochrome c oxidase, competitive with oxygen, is an intriguing mechanism to explain these findings

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