The mitochondrial permeability transition, an established mechanism for heart diseases, is a long-standing mystery of mitochondrial biology and a prime drug target for cardioprotection. Several hypotheses about its molecular nature have been put forward over the years, and the prevailing view is that permeabilization of the inner mitochondrial membrane follows opening of a high-conductance channel, the permeability transition pore, which is also called mitochondrial megachannel or multiconductance channel. The permeability transition strictly requires matrix Ca²⁺ and is favored by the matrix protein cyclophilin D, which mediates the inhibitory effects of cyclosporin A. Here we provide a review of the field, with specific emphasis on the possible role of the adenine nucleotide translocator and of the F-ATP synthase in channel formation, and on currently available small molecule inhibitors. While the possible mechanisms through which the adenine nucleotide translocator and the F-ATP synthase might form high-conductance channels remain unknown, reconstitution experiments and site-directed mutagenesis combined to electrophysiology have provided important clues. The hypothesis that more than one protein may act as a permeability transition pore provides a reasonable explanation for current controversies in the field, and holds great promise for the solution of the mystery of the permeability transition.

线粒体通透性转变是心脏病的既定机制，是线粒体生物学的一个长期谜团，也是心脏保护的主要药物靶标。这些年来，人们已经提出了几种关于其分子性质的假设，并且普遍的观点认为，线粒体内膜的通透性是随着高传导通道，通透性过渡孔（也称为线粒体大通道或多传导通道）的开放而发生的。渗透率转换严格要求基质Ca ²⁺并受到介导环孢菌素A抑制作用的基质蛋白亲环蛋白D的支持。在这里，我们提供对该领域的综述，特别着重于腺嘌呤核苷酸转运蛋白和F-ATP合酶在通道形成中的可能作用。 ，以及目前可用的小分子抑制剂。虽然腺嘌呤核苷酸转运蛋白和F-ATP合酶可能形成高传导通道的可能机制仍然未知，但重组实验和定点诱变与电生理学结合提供了重要的线索。一种以上的蛋白质可以充当通透性转变孔的假设为该领域当前的争议提供了合理的解释，并为解决通透性转变的奥秘提供了广阔的前景。