Membrane Deformation under Local pH Gradient: Mimicking Mitochondrial Cristae Dynamics
Membrane Deformation under Local pH Gradient: Mimicking Mitochondrial Cristae Dynamics
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DOI：
10.1529/biophysj.108.136077
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发表时间：
2008-11-15
影响因子：
3.4
通讯作者：
Angelova, Miglena I.
中科院分区：
文献类型：
--
作者：
Khalifat, Nada;Puff, Nicolas;Angelova, Miglena I.
线粒体是对细胞生命至关重要的细胞亚结构（细胞器），因为生物燃料的产生，即通过氧化磷酸化合成ATP，是在酸性（pH）梯度的驱动下发生的。线粒体在细胞死亡以及各种疲劳和运动不耐受综合征中也起着关键作用。现在清楚的是，线粒体呈现出惊人的多种内膜形态，与其功能状态动态相关，与ATP合成速率相结合，并且是正常和病理情况的特征。我们的工作提供了一些原始的见解的因素，决定动态管状结构的内膜嵴。我们显示了诱导的可能性，通过局部质子流，一个宏观的嵴状形状重塑的唯一的脂质膜。我们设计了一个最小的膜系统（GUV）和实验表明，定向调制的局部pH梯度在膜水平的含心磷脂囊泡诱导动态嵴样膜内陷。我们提出了一个机制和理论模型来解释所观察到的肾小管膜形态，并建议心磷脂的潜在作用。我们的研究结果支持本地化的生物能量转导的假设，并有助于显示嵴形态的内在能力，成为自我维持和优化ATP合成。
Mitochondria are cell substructures (organelles) critical for cell life, because biological fuel production, the ATP synthesis by oxidative phosphorylation, occurs in them driven by acidity (pH) gradients. Mitochondria play a key role as well in the cell death and in various fatigue and exercise intolerance syndromes. It is clear now that mitochondria present an astonishing variety of inner membrane morphologies, dynamically correlated with their functional state, coupled with the rate of the ATP synthesis, and characteristic for normal as well as for pathological cases. Our work offers some original insights into the factors that determine the dynamical tubular structures of the inner membrane cristae. We show the possibility to induce, by localized proton flow, a macroscopic cristae-like shape remodeling of an only-lipid membrane. We designed a minimal membrane system (GUV) and experimentally showed that the directional modulation of local pH gradient at membrane level of cardiolipin-containing vesicles induces dynamic cristae-like membrane invaginations. We propose a mechanism and theoretical model to explain the observed tubular membrane morphology and suggest the underlying role of cardiolipin. Our results support the hypothesis of localized bioenergetic transduction and contribute to showing the inherent capacity of cristae morphology to become self-maintaining and to optimize the ATP synthesis.