Of the two main sectors of the F-type ATP synthase, the membrane-intrinsic F_O domain is the one which, during evolution, has undergone the highest structural variations and changes in subunit composition. The F_O complexity in mitochondria is apparently related to additional enzyme functions that lack in bacterial and thylakoid complexes. Indeed, the F-type ATP synthase has the main bioenergetic role to synthesize ATP by exploiting the electrochemical gradient built by respiratory complexes. The F_O membrane domain, essential in the enzyme machinery, also participates in the bioenergetic cost of synthesizing ATP and in the formation of the cristae, thus contributing to mitochondrial morphology. The recent enzyme involvement in a high-conductance channel, which forms in the inner mitochondrial membrane and promotes the mitochondrial permeability transition, highlights a new F-type ATP synthase role. Point mutations which cause amino acid substitutions in F_O subunits produce mitochondrial dysfunctions and lead to severe pathologies. The F_O variability in different species, pointed out by cryo-EM analysis, mirrors the multiple enzyme functions and opens a new scenario in mitochondrial biology.

在F型ATP合酶的两个主要部分中，膜内源性F _O结构域在进化过程中经历了最高的结构变异和亚基组成变化。线粒体中的F _O复杂性显然与细菌和类囊体复合物中缺乏的其他酶功能有关。实际上，F型ATP合酶具有主要的生物能作用，可通过利用呼吸复合物建立的电化学梯度来合成ATP。酶机制中必不可少的F _O膜结构域，也参与了合成ATP的生物能成本和ista的形成。，从而有助于线粒体形态。最近的酶参与高传导通道，该通道在线粒体内膜中形成并促进线粒体通透性转变，突显了新的F型ATP合酶的作用。在F _O亚基中引起氨基酸取代的点突变产生线粒体功能障碍并导致严重的病理。冷冻-EM分析指出，不同物种的F _O变异性反映了多种酶的功能，并为线粒体生物学开辟了新的前景。