Modulation of the conformational state of mitochondrial complex I as a target for therapeutic intervention

We found that sensitivity of complex I to S-nitrosothiols and peroxynitrite is governed by the A/D status of the enzyme in vitro

Alexander Galkin; Salvador Moncada

2017

Scholarcy highlights

  • In recent years, there have been significant advances in our understanding of the functions of mitochondrial complex I other than the generation of energy
  • The only enzyme of the mitochondrial respiratory chain which catalyses the oxidation of matrix NADH by the respiratory chain is complex I or NADH:ubiquinone oxidoreductase
  • We found that sensitivity of complex I to S-nitrosothiols and peroxynitrite is governed by the A/D status of the enzyme in vitro
  • Impressive progress has been achieved in recent years in our understanding of the structure of mitochondrial complex I
  • The A/D transition of complex I can be considered an attractive target for modulation of complex I activity; it is still not clear what the driving force is for A/D transition and what subunits are involved in the conformational change
  • Further characterization of the A/D transition may provide a better understanding of the regulation of the mitochondrial response to oxygen deprivation and oxidative stress
  • It may help to develop novel therapeutic compounds for cardiovascular conditions, such as cardiac infarction, stroke and other ischaemia-associated pathologies

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