Visualizing Mitochondrial Fo F1 -ATP Synthase as the Target of the Immunomodulatory Drug Bz-423

Frontiers in Physiology
Ilka StarkeMichael Börsch

Abstract

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.

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Citations

Dec 22, 2019·Nature Communications·Nelli MnatsakanyanElizabeth A Jonas
May 29, 2020·Journal of Molecular and Cellular Cardiology·Nelli Mnatsakanyan, Elizabeth Ann Jonas
Jun 6, 2020·Toxicology in Vitro : an International Journal Published in Association with BIBRA·Abby HearneJeffrey S Wiseman

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Methods Mentioned

BETA
FRET
phage display
NMR
fluorescence microscopy
confocal
superresolution microscopies
confocal microscopy
superresolution microscopy

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