ReviewModifiers of the OLIGOMYCIN (cas 1404-19-9) sensitivity of the mitochondrial F1F0-ATPase

Add time:09/01/2019    Source:sciencedirect.com

The mitochondrial F1F0 complex is highly sensitive to macrolide antibiotics and especially targeted by OLIGOMYCIN (cas 1404-19-9)s. These compounds bind to the membrane-embedded sector F0 and block proton conductance through the inner membrane, thus inhibiting both ATP synthesis and hydrolysis. Oligomycin sensitivity is universally recognized as a clue of the functional integrity and matching between F0 and F1. Since oligomycin binding implies multiple interactions with amino acid residues of F0, amino acid substitutions often affect the inhibition efficiency. Moreover, variegated factors spanning from membrane properties to xenobiotic incorporation and detachment of the oligomycin-insensitive F1 sector can alter the oligomycin sensitivity of the enzyme complex. The overview on the multiple factors involved strengthens the link between altered oligomycin sensitivity and physiopathological conditions associated with defective ATPases. An improved understanding of the mechanisms involved may also favor drug design to counteract oxidative damage, which stems from most mitochondrial dysfunctions.

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