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Stretching tension effects in permeability transition pores of inner mitochondrial membrane
Biosystems ( IF 2.0 ) Pub Date : 2021-07-16 , DOI: 10.1016/j.biosystems.2021.104488
Igor Khmelinskii 1 , Vladimir Makarov 2
Affiliation  

Presently a mechanism of permeability transition pore (PTP) opening was proposed and discussed. This mechanism is based on mechanical stretching of inner mitochondrial membrane (IMM) caused by mitochondrial swelling (MS). The latter is induced by osmotic pressure generated by solute imbalance between the matrix and the surrounding cyto(sarco)plasm. Modelled by the Monte-Carlo method, an IMM fragment of 350 simulated biological molecules exhibited formation of micro-domains containing two protein and seven phospholipid molecules. The energies (−0.191 eV per molecule) in these micro-domains were significantly larger than those (−0.375 eV per molecule) of other parts of the IMM fragment. Stretching forces applied to such domains expanded them much more than other parts of the IMM fragment. We identify these micro-domains as the PTPs. Both linear and nonlinear functions were used for the strain-stress relation of the IMM fragment, with nonlinear effects more important at large IMM stretching strains. Thus, two main factors are incorporated into the PTP opening mechanism: (1) presence of micro-domains in the IMM structure and (2) IMM stretching stress caused by MS. Taking into account both of these factors, the equation for the probability of PTP opening was deduced, with matrix Ca2+ and H+ ionic concentrations as its parameters. Note that the equation deduced was similar to an earlier reported empirical equation describing PTP opening dynamics. This correspondence provides support to the presently proposed mechanism. Thus, a new look at the PTP opening mechanism is provided, of interest to various research areas related to mitochondrial biophysics.



中文翻译:

线粒体内膜通透性转换孔的拉伸张力效应

目前提出并讨论了渗透性过渡孔(PTP)的开放机制。该机制基于线粒体肿胀 (MS) 引起的线粒体内膜 (IMM) 的机械拉伸。后者是由基质和周围细胞(肌)质之间的溶质失衡产生的渗透压引起的。通过 Monte-Carlo 方法建模,350 个模拟生物分子的 IMM 片段表现出包含两个蛋白质和七个磷脂分子的微结构域的形成。这些微域中的能量(每分子-0.191 eV)明显大于IMM片段其他部分的能量(每分子-0.375 eV)。施加到这些区域的拉伸力比 IMM 碎片的其他部分扩展得更多。我们将这些微域识别为 PTP。线性和非线性函数都用于 IMM 片段的应变-应力关系,非线性效应在 IMM 大拉伸应变下更为重要。因此,两个主要因素被纳入 PTP 开放机制:(1)IMM 结构中存在微域和(2)由 MS 引起的 IMM 拉伸应力。考虑到这两个因素,推导出PTP打开概率方程,矩阵Ca2+和 H +离子浓度作为其参数。请注意,推导的方程类似于早期报道的描述 PTP 开放动力学的经验方程。这种对应关系为目前提出的机制提供了支持。因此,提供了对 PTP 开放机制的新看法,这对与线粒体生物物理学相关的各种研究领域很感兴趣。

更新日期:2021-07-19
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