线粒体通透性转换孔
生物
ATP合酶
细胞生物学
电压依赖性阴离子通道
线粒体
线粒体内膜
ATP-ADP转位酶
线粒体膜转运蛋白
胞浆
蛋白质亚单位
程序性细胞死亡
生物化学
线粒体凋亡诱导通道
内膜转移酶
内膜
细菌外膜
细胞凋亡
酶
大肠杆菌
基因
作者
Massimo Bonora,Angela Bononi,Elena De Marchi,Carlotta Giorgi,Magdalena Lebiedzińska,Saverio Marchi,Simone Patergnani,Alessandro Rimessi,Jan M. Suski,Aleksandra Wojtala,Mariusz R. Więckowski,Guido Kroemer,Lorenzo Galluzzi,Paolo Pinton
出处
期刊:Cell Cycle
[Informa]
日期:2013-02-15
卷期号:12 (4): 674-683
被引量:420
摘要
The term "mitochondrial permeability transition" (MPT) refers to an abrupt increase in the permeability of the inner mitochondrial membrane to low molecular weight solutes. Due to osmotic forces, MPT is paralleled by a massive influx of water into the mitochondrial matrix, eventually leading to the structural collapse of the organelle. Thus, MPT can initiate mitochondrial outer membrane permeabilization (MOMP), promoting the activation of the apoptotic caspase cascade as well as of caspase-independent cell death mechanisms. MPT appears to be mediated by the opening of the so-called "permeability transition pore complex" (PTPC), a poorly characterized and versatile supramolecular entity assembled at the junctions between the inner and outer mitochondrial membranes. In spite of considerable experimental efforts, the precise molecular composition of the PTPC remains obscure and only one of its constituents, cyclophilin D (CYPD), has been ascribed with a crucial role in the regulation of cell death. Conversely, the results of genetic experiments indicate that other major components of the PTPC, such as voltage-dependent anion channel (VDAC) and adenine nucleotide translocase (ANT), are dispensable for MPT-driven MOMP. Here, we demonstrate that the c subunit of the FO ATP synthase is required for MPT, mitochondrial fragmentation and cell death as induced by cytosolic calcium overload and oxidative stress in both glycolytic and respiratory cell models. Our results strongly suggest that, similar to CYPD, the c subunit of the FO ATP synthase constitutes a critical component of the PTPC.
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