线粒体膜完整性对细胞命运的调控

线粒体双层膜的完整性是细胞存活的关键因素，其遭到破坏后会使细胞发生凋亡、焦亡或炎症。线粒体膜的破坏包括线粒体外膜通透、线粒体内膜通透、通透性转换，三者可通过调控不同的信号通路导致不同的细胞命运。然而，这些信号通路之间存在交叉关联，使得线粒体膜对细胞命运的调控错综复杂，导致人们对其机制缺乏清晰的认识。本综述首先分析了不同程度线粒体外膜通透在细胞存活、癌变或凋亡中的作用，接着讨论了线粒体内膜通透通过引发线粒体DNA释放促进炎症发生的分子机制，然后阐述了线粒体通透性转换引发焦亡的作用机制，最后总结出线粒体膜完整性影响细胞命运决策的内在关联。深入了解线粒体膜完整性调控细胞命运的分子动力学机制，有助于为癌症和神经退行性疾病的诊疗提供思路。

The Roles of Mitochondrial Membrane Integrity in The Regulation of Cell Fate

Mitochondrial membrane integrity is so pivotal to cell survival that its damage can lead to apoptosis, pyroptosis or inflammation. The damage includes mitochondrial outer membrane permeabilization (MOMP), mitochondrial inner membrane permeabilization (MIMP), and mitochondrial permeability transition (MPT), which regulate different signaling pathways and thus lead to different cell fate outcomes. These signaling pathways are intersecting, which makes the involved mechanisms intricate and poorly understood. In this review, we firstly analysis the role of distinct degrees of MOMP in cell survival, tumorigenesis, and apoptosis, which may operate as a tristable switch. Then we discuss the molecular mechanism of MIMP in triggering inflammation through the release of mtDNA and envision that low order oligomers of Bak/Bax induce MOMP and promote apoptosis, while high order oligomers induce MIMP and cause inflammatory response. Furthermore, we clarify the working mechanisms of MOMP-induced apoptosis and MPT-driven pyroptosis under different stimulus intensities. Finally, we outline the intrinsic connection underlying cell-fate decision influenced by mitochondrial membrane integrity. Therefore, a deep understanding of the dynamical mechanisms of how mitochondrial membrane integrity regulates cell fate should give insight into the diagnosis and treatment of cancer and neurodegenerative diseases.