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

Ilka Starke; Gary D Glick; Michael Börsch

doi:10.3389/fphys.2018.00803

Visualizing Mitochondrial F_oF₁-ATP Synthase as the Target of the Immunomodulatory Drug Bz-423

Front Physiol. 2018 Jul 4:9:803. doi: 10.3389/fphys.2018.00803. eCollection 2018.

Authors

Ilka Starke^{1

2}, Gary D Glick³, Michael Börsch^{1

4}

Affiliations

¹ Single-Molecule Microscopy Group, Jena University Hospital, Friedrich Schiller University, Jena, Germany.
² Institute for Physical Chemistry, Albert Ludwigs University of Freiburg, Freiburg, Germany.
³ Department of Chemistry, University of Michigan, Ann Arbor, MI, United States.
⁴ Abbe Center of Photonics, Friedrich Schiller University, Jena, Germany.

Abstract

Targeting the mitochondrial enzyme F_oF₁-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 F_oF₁-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 F_oF₁-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: Bz-423; FRET acceptor photobleaching; FoF1-ATP synthase; Förster resonance energy transfer FRET; drug target; immunomodulator; mitochondria.

Publication types

Review