Department of Veterinary Medical Sciences, University of Bologna, Bologna, Italy.
Mitochondrion. 2013 Jul;13(4):312-9. doi: 10.1016/j.mito.2013.04.005. Epub 2013 Apr 16.
The mitochondrial F₁F₀ complex is highly sensitive to macrolide antibiotics and especially targeted by oligomycins. 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.
线粒体 F₁F₀ 复合酶对大环内酯类抗生素高度敏感，特别是对寡霉素类药物特别敏感。这些化合物与膜嵌入的 F₀ 部分结合，并阻断质子通过内膜的传导，从而抑制 ATP 的合成和水解。寡霉素敏感性被普遍认为是 F₀ 和 F₁ 之间功能完整性和匹配的线索。由于寡霉素结合暗示与 F₀ 的氨基酸残基有多种相互作用，氨基酸取代通常会影响抑制效率。此外，从膜性质到外来物质的掺入和寡霉素不敏感的 F₁ 部分的脱离等多种因素可以改变酶复合物对寡霉素的敏感性。对所涉及的多种因素的概述加强了改变的寡霉素敏感性与与功能障碍的 ATP 酶相关的生理病理条件之间的联系。对所涉及的机制的深入了解也可能有利于药物设计，以对抗源自大多数线粒体功能障碍的氧化损伤。
