Atomistic simulations indicate the c-subunit ring of the F1Fo ATP synthase is not the mitochondrial permeability transition pore

被引:65
|
作者
Zhou, Wenchang [1 ]
Marinelli, Fabrizio [1 ]
Nief, Corrine [1 ]
Faraldo-Gomez, Jose D. [1 ]
机构
[1] NHLBI, Theoret Mol Biophys Sect, NIH, Bldg 10, Bethesda, MD 20892 USA
来源
ELIFE | 2017年 / 6卷
关键词
HIGH-RESOLUTION STRUCTURE; ROTOR RING; ILYOBACTER-TARTARICUS; FORCE-FIELD; MECHANISM; OPTIMIZATION; DYNAMICS; CHANNEL; BINDING;
D O I
10.7554/eLife.23781
中图分类号
Q [生物科学];
学科分类号
07 ; 0710 ; 09 ;
摘要
Pathological metabolic conditions such as ischemia induce the rupture of the mitochondrial envelope and the release of pro-apoptotic proteins, leading to cell death. At the onset of this process, the inner mitochondrial membrane becomes depolarized and permeable to osmolytes, proposedly due to the opening of a non-selective protein channel of unknown molecular identity. A recent study purports that this channel, referred to as Mitochondrial Permeability Transition Pore (MPTP), is formed within the c-subunit ring of the ATP synthase, upon its dissociation from the catalytic domain of the enzyme. Here, we examine this claim for two c-rings of different lumen width, through calculations of their ion conductance and selectivity based on all-atom molecular dynamics simulations. We also quantify the likelihood that the lumen of these c-rings is in a hydrated, potentially conducting state rather than empty or blocked by lipid molecules. These calculations demonstrate that the structure and biophysical properties of a correctly assembled c-ring are inconsistent with those attributed to the MPTP.
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页数:11
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