Bioenergetic failure often features programmed cell death involved in some severe pathologies. When the cell is fated to die, the inner mitochondrial membrane becomes permeable to ions and solutes, due to the formation and opening of a channel known as mitochondrial permeability transition pore (mPTP). Up to now, the still‐elusive mPTP structure and mechanism prevented any attempt to identify/design drugs to rule its formation and limit cell death. Latest advances, which strongly suggest that the F₁F_O‐ATPase can coincide with the mPTP, open new perspectives in therapy. Compounds targeting and inhibiting cyclophilin D, a known mPTP promoter, could be exploited to block mPTP formation. Moreover, if the mPTP‐F₁F_O‐ATPase connection will be consolidated, selected F₁F_O‐ATPase inhibitors could represent novel therapeutic options to attenuate mPTP‐related diseases by directly acting on mPTP molecular mechanism. This intriguing perspective, which raises new hopes to counteract mPTP‐related diseases, stimulates further studies to clarify the mPTP architecture and mechanism.

中文翻译：

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线粒体通透性转变孔在细胞死亡：一种有前途的药物结合生物体系结构。

生物能衰竭通常表现为某些严重病理中涉及的程序性细胞死亡。当细胞注定要死亡时，由于称为线粒体通透性转换孔（mPTP）的通道的形成和开放，线粒体内膜对离子和溶质具有渗透性。到目前为止，仍然难以捉摸的mPTP结构和机制阻止了任何试图识别/设计药物以控制其形成并限制细胞死亡的尝试。最新的进展强烈暗示F ₁ F _O -ATPase可以与mPTP吻合，为治疗开辟了新的前景。可以利用靶向和抑制亲环蛋白D（一种已知的mPTP启动子）的化合物来阻断mPTP的形成。此外，如果mPTP‐F ₁ F _O‐ATPase连接将得到巩固，所选的F ₁ F _O ‐ATPase抑制剂可代表直接作用于mPTP分子机制来减轻mPTP相关疾病的新治疗选择。这种引人入胜的观点为对抗mPTP相关疾病提出了新希望，刺激了进一步的研究以阐明mPTP的结构和机制。