The Roles of Mitochondrial Membrane Integrity in The Regulation of Cell Fate [线粒体膜完整性对细胞命运的调控]

作者：Qi H.^*; Li Z.-C.; Shi Z.-Q.

来源：Progress in Biochemistry and Biophysics, 2022, 49(9): 1638-1647.

DOI：10.16476/j.pibb.2021.0271

• apoptosis
• inflammation
• mitochondrial inner membrane permeabilization
• mitochondrial outer membrane permeabilization
• mitochondrial permeability transition
• pyroptosis

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.

• 单位
  中国科学院大学; 山西大学