Frontiers in Physiology (Jul 2018)

Visualizing Mitochondrial FoF1-ATP Synthase as the Target of the Immunomodulatory Drug Bz-423

  • Ilka Starke,
  • Ilka Starke,
  • Gary D. Glick,
  • Michael Börsch,
  • Michael Börsch

DOI
https://doi.org/10.3389/fphys.2018.00803
Journal volume & issue
Vol. 9

Abstract

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Targeting the mitochondrial enzyme FoF1-ATP synthase and modulating its catalytic activities with small molecules is a promising new approach for treatment of autoimmune diseases. The immunomodulatory compound Bz-423 is such a drug that binds to subunit OSCP of the mitochondrial FoF1-ATP synthase and induces apoptosis via increased reactive oxygen production in coupled, actively respiring mitochondria. Here, we review the experimental progress to reveal the binding of Bz-423 to the mitochondrial target and discuss how subunit rotation of FoF1-ATP synthase is affected by Bz-423. Briefly, we report how Förster resonance energy transfer can be employed to colocalize the enzyme and the fluorescently tagged Bz-423 within the mitochondria of living cells with nanometer resolution.

Keywords