IBiTech - BioMMedA research group, Ghent University, Ghent, Belgium.
Adv Exp Med Biol. 2024;1463:271-275. doi: 10.1007/978-3-031-67458-7_45.
The "oxygen paradox" embodies the delicate interplay between two opposing biological processes involving oxygen (O). O is indispensable for aerobic metabolism, fuelling oxidative phosphorylation in mitochondria. However, excess O can generate reactive species that harm cells. Thus, maintaining O balance is paramount, requiring the prioritisation of its benefits while minimising potential harm. Previous research hypothesised that caveolae, specialised cholesterol-rich membrane structures with a curved morphology, regulate cellular O levels. Their role in absorbing and controlling O release to mitochondria remains unclear. To address this gap, we aim to explore how the structural features of caveolae, particularly membrane curvature, influence local O levels. Using coarse-grained (CG) molecular dynamics simulations, we simulate a caveola-like curved membrane and select a CG bead as the O model. Comparing a flat bilayer and a liposome of 10 nm diameter, composed of 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC), allows us to study changes in the O free energy profile. Our findings reveal that curvature has a contrasting effect on the free energy of the outer and inner layers. These findings show the membrane curvature's impact on O partitioning in the membrane and O permeation barriers, paving the way towards our understanding of the role of caveolae curvature in O homeostasis.
“氧气悖论”体现了涉及氧气 (O) 的两种对立生物过程之间的微妙相互作用。O 对于需氧代谢是不可或缺的，为线粒体中的氧化磷酸化提供动力。然而，过量的 O 会产生伤害细胞的活性物质。因此，维持 O 的平衡至关重要，需要在优先考虑其益处的同时最大限度地减少潜在的危害。先前的研究假设 caveolae（一种具有弯曲形态的富含胆固醇的特殊膜结构）调节细胞内的 O 水平。其在吸收和控制 O 向线粒体释放方面的作用仍不清楚。为了解决这一差距，我们旨在探索 caveolae 的结构特征（特别是膜曲率）如何影响局部 O 水平。使用粗粒化 (CG) 分子动力学模拟，我们模拟了 caveola 样弯曲膜，并选择 CG 珠作为 O 模型。通过比较平坦的双层膜和由 1-棕榈酰基-2-油酰基-sn-甘油-3-磷酸胆碱 (POPC) 组成的直径为 10nm 的脂质体，我们可以研究 O 自由能曲线的变化。我们的研究结果表明，曲率对内外层的自由能具有相反的影响。这些发现表明膜曲率对 O 在膜中的分配和 O 渗透屏障有影响，为我们理解 caveolae 曲率在 O 稳态中的作用奠定了基础。
